Marine organisms: Pioneer natural sources of polysaccharides/proteins for green synthesis of nanoparticles and their potential applications

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Introduction
Nanotechnology is a scientific field that involves the engineering of the materials/molecules or atoms at the nanoscale level (1-100 nm) via top-down or bottom-up strategies [1].The recent development of nanotechnology field has resulted in the fabrication or synthesis of various nanostructures among them nanoparticles (NPs), nanomaterials, nanocapsules, nanotubes, nanocarriers, nanosheets, nanocolloids, nanoflakes, quantum dots (QDs) and nanocomposites [2].
Nanotechnology can provide nanostructures with unique physicochemical, electrochemical, and biological properties.Nanostructures have ultrasmall sizes, combined with high surface-to-volume ratios, and often display other desirable properties such as the presence of biochemical moieties on their surface, surface charges, a hydrophilic or hydrophobic nature and the ability to be manufactured in various shapes and morphologies [3].
Metallic and nonmetallic NPs with specific sizes, morphologies and unique characteristics are synthesized or engineered via several physical and/or chemical procedures.These approaches employ toxic, nonbiodegradable and expensive chemicals as reducing and capping agents that have undesirable effects on the environment and in biological systems [16].Therefore, there is an urgent call to develop reliable, efficient and eco-friendly procedures for the synthesis NPs and nanocomposites [17].
Since the oceans cover almost 70% of the Earth's surface, they represent the most diverse ecosystem on our planet.Scientists are exploring this diversity by identifying and isolating marine organisms, thereby revealing a novel branch of research and application known as blue biotechnology [18].The marine ecosystem represents an environment with one of the most widely varying conditions in terms of light, temperature, pressure, and nutrient status.In addition, the association of marine organisms with their aquatic habitat often culminates in the generation of variable complex and unique chemical structures that are secreted by them to improve their competitiveness and chances of survival [19].Notably, these metabolites exhibit a wide range of applications i.e., in industry, medicine, drug delivery, and nanotechnology, etc. [19,20].
Marine bio-nanotechnology is one of the most promising biotechnologies and scientific research fields today owing to the unique fusion of marine biotechnology and the nanotechnology fields [21].Various marine organisms (macro/microalgae, seaweeds, bacteria, actinomycetes, cyanobacteria, fungi, soft corals, invertebrates, vertebrates, sponges and plants) play exciting roles in the green/eco-friendly fabrication of NPs, possessing unique characteristics and having numerous potential applications [22].Notably, these organisms are often rich in various biological constituents, among them are proteins, polypeptides, carbohydrates, polyphenols, polysaccharides, polymers, alkaloids, and pigments [23], and could be employed as potential bioreducing, capping and stabilizing agents in one-step bioengineering of nanostructures including NPs [24] (Fig. 1).
Many of the NPs capable of being sourced from marine organisms, such as Ag, Au, Pd, Cd, Ru, iron oxide, cobalt oxide, zinc oxide and carbon quantum dots (QDs), maybe exploited in medicinal applications including bioimaging and biolabeling [25], cancer therapy and drug delivery [26], sensors [27], as well as antibacterial, antidiabetic, antioxidant for AuNPs [28], antiviral [29], antifouling activities for AgNPs [30].This review critically assesses the potential of NPs biosynthesized from extracts or polymers originating from marine organisms, the mechanism of synthesis, as well as their characteristics and significant biomedical/industrial applications.

Marine plants (seagrasses/mangroves)
Marine plants, known as seagrasses, are flowering plants that form underwater meadows.They play a crucial role in global food security, mitigation of climate change and conservation of biodiversity around the world [31].As marine plants are crucial sources of important bioactive constituents, they can be employed as beneficial candidates for the green fabrication of metallic NPs [32,33].For instance, Palaniappan et al. studied and discussed the role of the seagrass, Cymodocea serrulate in the biosynthesis of silver (Ag) NPs.In their study, 5 mL of an aqueous extract of seagrass was added to 95 mL of an aqueous solution of silver nitrate (1 mM).The bioproduction of Ag + into Ag 0 , as well as the biosynthesis, capping and stabilization of AgNPs are accounted to the metabolic profile of the seagrass that consists of protein, tannin, sterol, and alkaloids.The cytotoxic potential of these particles was assessed against lung cancer cells, whereby the synthesized NPs at 250 and 100 μg/mL were shown to cause cellular components and cell death in >80% and ~50% of the cancer cells, respectively [34].
Halophila stipulacea, another seagrass has been utilized to fabricate Ag and iron oxide NPs.For the biofabrication of AgNPs, 10 mL of an aqueous extract of H. stipulacea was added to 90 mL of a 1 mM AgNO 3 solution in a 250 mL conical flask and mixed for 48 h at 120 rpm.While for generation of Fe 2 O 3 NPs, a solution of FeCl 3 (0.1 M) was added to the H. stipulacea aqueous extract in a ratio of 1:1 (v/v) and mixed for 90 min.Although FTIR spectra confirmed that the polyphenols, flavonoids, and carbohydrates (polysaccharides) were responsible for the biogeneration of AgNPs, protein and amides were found to be the key components involved in the biofabrication of Fe 2 O 3 NPs.Moreover, the anti-algal efficiencies of AgNPs and Fe 2 O 3 NPs against Oscillatoria simplicissima had been studied (Table 1) [35].
Ahila et al. synthesized silver NPs using the marine seagrass, Syringodium isoetifolium by blending 5 mL of an aqueous S. isoetifolium extract with 95 mL of 1 mM silver nitrate at 45 • C. The reaction mixture color changed from transparent pale green to reddish-brown and Surface Plasmon Resonance (SPR) spectra at 422 nm confirmed the presence of AgNPs.Subsequently, the TEM spectra revealed the size of the NPs to be 2-50 nm and their morphology to be polydispersed spherical in shape and crystalline in nature.On the basis of FTIR analysis, it was proposed that proteins and amino acids play a dual role as reducing as well as capping agents [36].
Another marine plant, Rhizophora mucronate, (a mangrove), has been shown to exhibit biosynthesis and capping of AgNPs.An aqueous solution of silver nitrate (0.001 M) was stirred with an aqueous extract of the plant in a 4:1 ratio to afford up to 100 mL volume for 24 h.Subsequently, the color of the mixture was adjusted from light yellow to dark brown because of the reduction of Ag + in the formation of AgNPs, (their synthesis being confirmed by surface plasmon resonance (SPR) spectra at 460 nm).Certain antifungal drugs e.g., fluconazole and itraconazole have been shown to demonstrate superior antifungal activity toward Candida albicans, Aspergillus fumigatus, A. flavus and Cryptococcus neoformans when used in combination with the biosynthesized AgNPs [33].

Marine algae (micro/macro algae)
Marine algae are photosynthetic aquatic species comprising different genera, mainly classified into two groups, namely, macroalgae and microalgae.Macroalgae (seaweeds) are plant-like organisms that are a few centimeters to several meters long.Conversely, microalgae represent the survival phytoplankton, which are generally ranging between 1 μm to 2 mm length suspended in the water column [37,38].Many bioactive constituents and polymers such as carbohydrates, proteins, alginates, carrageenan, laminaran, fucoidan, lipids, fatty acids and phenolic compounds represent the major constituents of algae [39].Several recent studies have confirmed that these bioactive constituents and polymers play significant roles in the green biosynthesis of a wide variety of metallic and nonmetallic NPs.For example, Gelidium corneum, a red marine alga has been recently utilized in the eco-friendly biosynthesis of AgNPs employing silver nitrate as a precursor salt, generating spherical and angularly crystalline AgNPs with a centric cubic geometry (particle size, 20-50 nm) as detected by XRD and TEM.Additionally, the FTIR analysis indicated that azo compounds and oxidation of the aldehyde group might be a key to the bio-reduction of AgNO 3 to AgNPs.The antibacterial and antibiofilm activities of these particles against C. albicans and E. coli microorganisms were evaluated by Broth microdilution [40].
Trichodesmium erythraeum, another microalga has been employed to biosynthesize AgNPs whereby, ~ 5 g of the algal biomass was extracted with 50 mL of Milli-Q water.5% (v/v) of the algal extract was gradually added to 1 mM of AgNO 3 to biosynthesize AgNPs with an average size of 26.5 nm ascribed to the reduction of Ag + to Ag 0 (Fig. 1).Various techniques were applied to characterize these NPs, among them were UV-Vis spectroscopy, FTIR, SEM, AFM, EDX, and XRD.Importantly, the AgNPs obtained exhibited potential antioxidant, antibacterial and antiproliferative activities [41].Another study reported the biofabrication of stable colloidal crystalline AgNPs utilizing the marine green alga Caulerpa serrulate.TEM showed the fabricated NPs to be 10 ± 2 nm in size with a spherical shape.Moreover, they displayed photocatalytic activity, achieving a 99% degradation of Congo red dye after 6 min of incubation time.Additionally, they exhibited antibacterial activity against Staphylococcus aureus, Shigella sp., Salmonella typhi, and Escherichia coli (Gram-negative), and Pseudomonas aeruginosa (Gram-positive) bacteria [42].Methylene blue (MB) is another complex dye, very toxic to living organisms; thus, its degradation is an environmentally and biologically urgent issue.In this context, Edison et al. employed the marine green alga, Caulerpa racemosa to biogenerate AgNPs that were capable of completely degrade MB after 30 min in the presence of NaBH 4 at a constant rate of 1.114 × 10 − 3 s − 1 under light conditions.Highresolution TEM (HR-TEM) analysis affirmed the spherical shape and a particle size of 25 nm and XRD revealed its crystalline nature [43].In a similar study, the antibacterial activity of the resultant silver nanoparticles that were fabricated using the same alga was tested against Staphylococcus aureus and Proteus mirabilis using the well-diffusion method [44].
A sulfated polysaccharide isolated from the marine red algae Porphyra vietnamensis was investigated as a bioactive molecule for the biosynthesis of AgNPs by adding it to silver nitrate.The average size of the NPs produced was 13 ± 3 nm and they were reported as a potent antibacterial agent against Gram-negative and Gram-positive bacteria [45].Furthermore, the polysaccharides isolated from different marine macroalgae (Pterocladia capillacae, Jania rubins, Ulva faciata, and Colpmenia sinusa) that collected from the coast of Abo-Qire, Alexandria, Cairo, Egypt were utilized to biosynthesize, cap and stabilize sphereshaped AgNPs with an average size of 7-20 nm.The NPs generated shared good activity against the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacterium E. coli at 108 ppm [46].Shakibaie et al. reported the extracellular biosynthesis and characterization of gold nanoparticles (AuNPs) by employing a chloroauric acid (HAuCl 4 ) solution and an aqueous extract of the marine microalga (Tetraselmis suecica).The UV-Vis spectra revealed a clear band at 530 nm corresponding to the fabrication of AuNPs.Their diameter was 51-120 nm but the most frequent one was 79 nm with a spherical shape, polydispersed and crystalline structure [47].Padina gymnospora, a marine brown alga, was utilized to biosynthesize AuNPs and it was reported that the hydroxyl groups of the algal polysaccharides were involved in the gold bioreduction.Notably, X-ray diffraction (XRD) results confirmed the crystalline nature of the fabricated NPs, and AFM analysis displayed that the particles sized within 53 to 67 nm [48].
Ramakrishna et al. separately employed the aqueous extracts of two marine algae (Sargassum tenerrimum and Turbinaria conoides) as reducing agents of gold ions.Interestingly, the gold nanoparticles produced from the two extracts exhibited photocatalytic activity by degradation of 4nitrophenol and p-nitroaniline into their corresponding aminoarenes (4-aminophenol and p-phenylenediamine) and by rendering naturally colored solutions (Rhodamine B and Sulforhodamine) into colorless solution in the presence of NaBH 4 as a catalyst [49].
Babu et al. have reported the bioengineering of gold nanoparticles using the marine seaweed Acanthophora spicifera.FE-SEM, HR-TEM, EDAX and DLS revealed that the AuNPs have average particles size < 20 nm, crystallinity, spherical-to-oval shapes, as well have an average hydrodynamic diameter and zeta value of 874.3 and − 35.8 mV respectively, indicating that the gold NPs have a good stability.Additionally, the antibacterial, cytotoxic and antioxidant of these gold nanoparticles displayed good activities against Vibrio harveyi, Staphylococcus aureus, HT-29, 2,2-diphenyl-1-picrylhydrazyl (DPPH) and NO 2 radicals respectively [50].
Azizi et al. studied the production of zinc oxide nanoparticles using the marine brown algae, Sargassum muticum.A change in the color of their reaction from dark brown to pale white indicated the generation of ZnONPs, and FTIR spectra revealed that the sulfate and hydroxyl moieties of the polysaccharide might be the biomolecules responsible for the reduction, capping and stabilization of the biosynthesized ZnONPs [51].
Zirconia nanoparticles (ZrO 2 ) are important nanomaterials characterized by their good biocompatibility, mechanical strength, strong resistance to corrosion, as well possessing a wide range of applications in synthesizing refractories, foundry sands, ceramics and biomedical fields, including biosensors, cancer therapy, implants, joint endoprosthesis, and dentistry [52].For example, Kumaresan et al. synthesized (ZrO 2 ) nanoparticles using a green eco-friendly method by employing the marine seaweed Sargassum wightii as a reducing, capping and stabilizing agent.The XRD pattern indicates the biosynthesized NPs to be crystalline with a diameter of 4.8 nm.FTIR spectra revealed that carboxylate ions might have stabilized the fabricated zirconia NPs.Furthermore, the antibacterial activity of the formed NPs against various types of Gramnegative and Gram-positive bacteria, among them Bacillus subtilis, E. coli and S. typhi was evaluated [53].
Chaetomorpha is a marine green alga possesses excess content of chlorophyll, polyphenols, and meroterpenoid which are the key of the reduction and stabilization of Ag + to AgNPs and Ag@AgClNPs, using several intermolecular interactions.These nanoparticles have the potential to be used as an interesting sensor for detecting hazardous Hg 2+ in water [27].
Fucoidan is a naturally sulfated polysaccharide polymer that can be isolated from some aquatic species (Fucus vesiculosus; seaweed).Fucoidan is a useful bioreducing agent used for example, in the biosynthesis of AuNPs.The Fu-AuNPs biofabricated using fucoidan have been shown to exhibit unique biocompatible properties, and have been employed in doxorubicin (DOX) drug delivery and as a cytotoxic agent (Table 2) [26].

Marine cyanobacteria
Marine cyanobacteria (blue-green algae) constitute a valuable group of ancient photosynthetic filamentous prokaryotic microorganisms, occupying several habitats ranging from oceans to freshwaters.They are responsible for producing a large fraction of the atmospheric oxygen, and they produce a surprising variety of secondary metabolites [88].According to Tan and Phyo, thus far, 550 bioactive compounds have been reported from marine cyanobacteria genera.Generally, most of these compounds are nitrogen-containing metabolites that are synthesized through either non-ribosomal peptide synthetase (NRPS) or polyketide synthetase (PKS) and hybrid NRPS-PKS biosynthetic pathways [89].Therefore, marine cyanobacteria serve as a rich source of promising secondary metabolites with potential technological applications in the field of nanotechnology, which are attracting increasing the interest in these research disciplines.
Oscillatoria princeps, a marine cyanobacterium (blue-green alga) is a very rich source of alcohol, carboxylic acid, amine, oxime, and nitrogen compounds.It is employed to bioengineer AgNPs.When 1 mL of AgNO 3 (1 mM) solution was added to an aqueous solution of the alga, the color of the solution changed from pale green to deep brown.The color change was confirmed by UV-Visible spectra at 200-750 nm, which confirmed the formation of AgNPs.The synthesized AgNPs demonstrated potential antibacterial activity against S. pyogenes and E. coli with inhibition zone sizes of (14-16) mm using the agar well-diffusion method [90].In a similar study by Hamouda et al. another marine cyanobacterium, Oscillatoria limnetica, was utilized for the biomimicry, capping and stabilization of AgNPs.After an aqueous extract (5 mL) of cyanobacterium aqueous extract was added to 1 mL of AgNO 3 aqueous solution at 35 • C, the color changed from green to dark brown, demonstrating the biotransformation of Ag + to Ag 0 with generation of NPs confirmed by SPR spectra at 426 nm as illustrated by UV spectra.As confirmed by FTIR spectra, the amide, amine and hydroxyl constituents contributed to the bioreduction, capping and stabilization of the AgNPs.Concurrently, the TEM and SEM micrographs revealed the morphology,             nature and size of the biosynthesized AgNPs to be quasi-spherical and anisotropic with a size of 3.30-17.97nm.The cytotoxic and antimicrobial activities of the AgNPs against breast, colon cancers and multi-drug resistant bacteria (E. coli and B. cereusbeen) were also reported [91].

Marine bacteria
The marine environment is a rich source of large and small biologically interesting molecules.Marine bacteria, in particular, attract the attention of researchers owing to their ability to synthesize complex structurally diverse classes of bioactive secondary metabolites [93].Alkaloids, steroids, terpenoids, peptides, and polyketides are considered the major secondary metabolites of marine bacteria.Recent studies have indicated that 10%-20% of bacteria isolated from marine habitats exhibit properties suited to biotechnological, pharmaceutical, therapeutic and nanotechnological applications [94].For instance, the marine bacterium Marinobacter pelagius has been utilized in the eco-friendly green fabrication of AuNPs.Washed marine bacteria cells (10 mg wet/ wt.basis) were added to 10 mL of an aqueous solution of HAuCl 4 at a concentration of 250 mg/L.The resulting NPs were characterized using TEM, dynamic light scattering (DLS) and UV-Vis spectroscopy revealing their size (2− 10) nm and shape (spherical and/or triangular) [95].
Furthermore, Streptomyces rochei, a marine cyanobacterium, has been utilized for the extracellular bioreduction of AgNO 3 at two different concentrations (1 and 0.1 mM) to produce AgNPs.The NPs produced from a 10 − 4 M concentration of AgNO 3 displayed better antibacterial activity against S. aureus and P. aeruginosa than NPs from the molar concentration of 10 − 3 [96].
Abd-Elnaby et al. studied the biosynthesis of AgNPs utilizing the marine bacterium, Streptomyces rochei MHM13 collected from the sediment of the Suez Gulf, the Red Sea, Egypt.Bacterial supernatant (50 mL) was mixed with 50 mL of AgNO 3 (1 mM) to produce spherical NPs with a size of 22-85 nm.The FTIR chromatogram affirmed that the amide groups of the proteins were able to bind and cap the synthetic NPs.These biosynthesized NPs demonstrated good antibacterial activity toward numerous bacteria; among them were Vibrio fluvialis, Pseudomonas aeruginosa, Salmonella typhimurium, Vibrio damsela, E. coli, Bacillus subtilis, Staphylococcus aureus and B. cereus.There was a potential synergetic effect when the NPs were used in combination with six standard antibiotics (ciprofloxacin, ampicillin, streptomycin, gentamicin, tetracycline and lincomycin) versus the antibiotics alone and they prevented the development of resistant pathogenic microbes and improved the antimicrobial characteristics of the antibiotics.Similarly, a cytotoxic effect was demonstrated against HepG2, HCT-116, MCF-7, PC-3, A-549, CACO, HEP-2 and HELA cell lines by employing a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay [97].
On the other hand, Hamed et al., performed an extracellular ecofriendly synthesis of AgNPs using the supernatants of two actinomycetes strains (Streptomyces sp.192ANMG and Streptomyces sp.17ANMG), which were isolated from Crella cyathophora, a marine sponge.It was assumed that the amino and carboxylic acids of the actinomycete were responsible for the bio-reduction of AgNO 3 to AgNPs.The generated NPs from the two strains also exhibited antibacterial, anti-biofilm and cytotoxic properties against various types of bacteria and cancer cell lines [98].
Furthermore, Scara et al. demonstrated that some exopolymers i.e., EPS B3-15, EPS T14 and the poly-γ-glutamic acid γ-PGA-APA that were extracted from marine bacteria namely, Bacillus licheniformis strain B3-15, B. licheniformis strain T14 and B. horneckiae strain APA serve as good bioreducing agents for biofabrication AuNPs and AgNPs.Both EPS B3-15 and EPS T14 possess higher carbohydrates and proteins contents compared with γ-PGA-APA, thus, EPS B3-15 and EPS T14 have the potential to biosynthesize silver and gold nanoparticles without any reducing agent.But γ-PGA-APA failed to synthesize silver and gold nanoparticles, so NaBH 4 was added as a catalyst.The antimicrobial properties of the prepared noble NPs were evaluated against various types of bacteria and fungus including S. aureus, E. coli, P. aeruginosa, and C. albicans [17].
Ag 2 O/AgNPs could be biofabricated as well by adding 100 mL of Streptomyces sp.VITSTK7, (a marine bacterium) supernatant to 200 mL of AgNO 3 (1 mM) under dark conditions for 1 week at 30 • C. The color of the mixture changed from yellow to dark brown and the formation of SPR bands at 420 nm during the reaction period affirmed the generation of Ag 2 O/AgNPs.TEM, AFM and XRD chromatograms confirmed the spherical and crystalline shapes and sizes of the resultant nanoparticles at 27.9-34.2nm.The nanoparticles exhibited antifungal properties against Aspergillus niger, A. flavus and A. fumigatus with an antifungal index of 62%-75% [99].
An exopolysaccharide that was isolated from the marine bacterium, Streptomyces violaceus MM72 was shown to promote the biosynthesis of AgNPs whereas the carbohydrate, ash, and moisture contents of this exopolysaccharide were 61.4%, 16.1% and 1.8% respectively.The silver nanoparticles obtained were of size of 10-100 nm with a spherical shape, and they exhibited antibacterial activity when was tested using the disc diffusion method against E. coli, Pseudomonas aeruginosa, S. aureus and B. subtilis bacteria [100].Fucoidanase is an enzyme that has been reported from certain marine organisms only to date.Fucoidanase hydrolyze fucoidan (a sulfated polysaccharide) to afford sulfated low-molecular-weight fucoidan without removing its side substitute groups.In this context, Manivasagan studied the potential effect of fucoidanase on the synthesis of AuNPs, whereby 1 mL of purified fucoidanase was added to 10 mL of an aqueous solution of gold chloride (1 mM) for 30 min at 80 • C. Subsequently, the color change to intense pinkish ruby red indicated the generation of AuNPs with an SPR band on UV spectra at 531 nm (Table 4) [101].
Bacillus sp.MSh-1, a newly identified species of marine bacterium, has been employed for the green synthesis of SeNPs.Fresh inocula of bacteria (1 mL) were mixed with 1.26 mM Se 2 O and incubated in a shaker incubator (150 rpm) for 14 h.at 30 • C. Following the formation of Se 0 , the solution color changed to orange-red.TEM and SEM images clearly illustrated the spherical shape of the NPs and a size range of 80-220 nm.Importantly, the biogenic nanoselenium demonstrated antioxidant and cytotoxic activities toward DPPH radical scavenging activity and the MCF-7 cell line, respectively [102].
In addition to their exploitation for the eco-friendly biosynthesis of NPs, marine bacteria are also employed to synthesize QDs.For example, two marine bacteria (Bacillus pumilus and Serratia marcescens) have been employed for the first time to biosynthesize cadmium telluride (CdTe) QDs on the surface of bacteria cells.UV-Vis spectroscopy, XRD, DLS, photoluminescence (PL), SEM and EDS analyses confirmed the generation of cubic CdTe QDs (10 nm) and characterization of their fluorescence properties, confirmed them as effective bioinspired nanostructures for potential biolabeling purposes of yeast and cancer cells, etc. [25].

Marine fungi
Marine fungi are globally distributed in the oceans and are associated with marine sediments and organisms such as plants, algae, soft corals and sponges.According to Balabanova et al., around 1112 marine fungus species within 472 genera have been isolated and identified to date [119].Approximately, 60% of the recorded marine fungi are obligatory marine species that undergo several physiological plasticity processes that allow many taxa to flourish in both freshwater and marine habitats [120].The metabolites of marine fungi have caught the limelight in numerous applications, including drug discovery and nanobiotechnology [121,122].
Aspergillus sydowii, a marine fungus, was studied for the first time in the synthesis of AuNPs using 3 mM HAuCl 4 salt.Herein, the solution color changed from yellow to purple-lavender and pink in parallel with the nanoparticle's sizes and concentrations of exposed gold chloride.A decrease in particles sizes was observed with an increase in gold salt concentration.The nanoparticles were 8.7-15.6 nm in size and spherical in shape, as shown by TEM [123].Vala et al. as well studied the green biosynthesis of AgNPs using a marine fungus (Aspergillus niger).Separately, 5 g of the fungus biomass was added to 100 mL of silver nitrate solution at various concentrations (0.25, 0.5 and 1.0 mM).After 72 h. of incubation, the color of the solution changed from colorless to pink, generating an SPR band at 425 nm confirming the formation of silver nanoparticles.Additionally, TEM confirmed their spherical shape and size of 5-26 nm [124].
Another species, Aspergillus brunneoviolaceus, has demonstrated proficiency in the biogenic synthesis of silver NPs based on its possession of various biomolecules, including alcohols, phenols, sulfur, amines, and nitro compounds, that play an effective role in the biogeneration of silver nanoparticles.On the basis of the XRD and TEM analyses, the morphology of these particles showed a spherical shape with facecentered cubic packing and a size of 1.4 ± 0.8 nm.The AgNPs produced were reported to be good candidates for the inhibition of certain Gram-negative and Gram-positive bacteria e.g., B. subtilis, S. aureus, P. aeruginosa, E. coli, and Salmonella spp. as well as having antioxidant potential toward DPPH free radicals [122].
With the aid of the marine fungus (Penicillium polonicum ARA 10) isolated from the marine green alga, Chetomorpha antennina, Neethu et al. performed extracellular biosynthesis of AgNPs.Raman spectra indicated that protein molecules were responsible for the reduction, capping and stability of the generated AgNPs.The antibacterial properties of these spherical crystalline NPs against Salmonella typhimurium were assessed using the well-diffusion method with a minimum bactericidal concentration (MBC) of 15.62 μg/mL [125].The biofabrication of AuNPs from P. polonicum MF185681 was studied by Neethu et al.Fungal cell filtrate (10 mL) was added to 90 mL of AgNO 3 (1 mM) to generate spherical NPs.The color of the solution changed to dark brown, attributed to the formation of Ag nanoparticles, as further demonstrated by an absorption peak at 430 nm in UV spectra.It is noteworthy that FTIR and Raman spectra confirmed the enclosed sulfur-containing amino acids and the aromatic amino acids played a potential role in the bioreduction of silver ions to spherical and crystalline silver NPs of size 10-15 nm.The obtained NPs showed antibacterial efficacy against a multidrugresistant strain of the bacterium, Acinetobacter baumanii [126].
Manjunath et al. employed an aqueous extract of the marine endophytic fungus, Penicillium citrinum for the extracellular biogenic synthesis of AuNPs by mixing an aqueous filtrate of the fungus with 1 mM AuCl 4 .FTIR results affirmed that the fungus flavonoids and proteins were responsible for the bioreduction, capping and stabilization of the AuNPs.DLS, XRD and FESEM analyses determined the spherical shape and crystalline nature of the formed AuNPs within and a size of 60-80 nm.The antioxidant potential of the AuNPs against DPPH radicals was also reported as well [127].Researchers added an enzyme/protein (180 μg/mL) extracted from the fungus Trichoderma harzianum (originally obtained from a wetland ecosystem, (in Gangwon-Do, South Korea) to 15 mL of chitosan (CS) solution under magnetic stirring for 30 min and found that this led to the development of CSNPs that absorbed UV light at 280 nm.Particle-size analysis (PSA) indicated a range of 10-314 nm (mean 46 nm).The bactericidal and biocompatibility activities of these particles were also investigated (Table 5) [128].

Marine yeasts
Marine yeasts are microorganisms that grow better in seawater than in freshwater.Bernhard Fischer was the first to isolate yeast from the Atlantic Ocean in 1894.Marine yeasts may be parasitic, mutualistic, saprophytic, or commensal and may occupy a wide range of habitats, including seaweeds, marine invertebrates, sea sediments, seawater, vertebrates, and mangrove biomes [130].Since marine yeasts exhibit a strong tendency to thrive under extreme conditions, they must demonstrate versatile potential for the synthesis of functional biomolecules,  including enzymes, proteins, bioactive constituents, fine chemicals and NPs with a wide range of applications in various fields encompassing food, chemicals, agriculture, biofuels, biomedicine and nanotechnology [131].
Rhodosporidium diobovatum, a marine yeast was employed by Seshadri et al. to intracellular synthesize stable semiconductor nanoparticles (lead sulfide NPs).UV spectra revealed a peak at 320 nm corresponding to PbSNPs, and their morphology (spherical cubic structure) and size (2-5) nm were determined via XRD and Energy Dispersive X-Ray Analysis (EDAX).EDAX elemental analysis also confirmed a 1:2 ratio of lead to sulfur, reflecting the fact that the PbSNPs were capped by a sulfur-rich peptide.Importantly, during the intracellular synthesis, the size of the PbSNPs was stable for more than six months, this being attributed to the adaptive stress responses of yeasts, such as sequestration by the small thiol tripeptide glutathione or phytochelatins upon exposure to oxidative stress and metals [132].
Yarrowia lipolytica (NCYC 789) is a psychrotrophic marine strain of ascomycetous yeast.Yeast cell suspensions and their extracted melanin have been utilized for intracellular and extracellular silver nanoparticles synthesis, respectively.The XRD pattern revealed the face-centered cubic structure of the silver particles indexed to ( 111), ( 200) and (220) (JCPDS Card No. 04-0784), and SEM images confirmed the accumulation of silver NPs on the surfaces of the cells where Ag + ions were reduced to Ag 0 .FTIR results showed that enclosed phenolic, hydroxyl and amino groups were responsible for the generation of NPs.As confirmed by SEM and TEM analysis, the melanin mediated AgNPs were spherical in shape, were of a monodispersed nature and were 15 nm in size.Additionally, they exerted 37% and 67% antibiofilm activities against S. paratyphi MTCC 735 after incubation for 24 and 48 h., respectively [133].
Additionally, Pimprikar et al. conduct experimental research to examine the ability of a various number of marine yeast (Yarrowia lipolytica NCIM 3589) cells to biomimetic AuNPs when incubated with different concentrations (0.5, 1.0, 2.0, 3.0, 4.0 or 5.0 mM) of HAuCl 4 .The generation of gold NPs changed the color of the mixture to purple or golden red whereas the size of the obtained AuNPs or nanoplates differed according to the variation in the number of yeast cells and concentration of gold salt.However, with the increasing yeast cell numbers with a constant gold salt concentration, the size of nanoparticles decreased to between 9 and 27 nm.The FTIR spectra also affirmed the possible involvement of amide carboxyl and hydroxyl groups on the surface of the cells during NPs synthesis [134].
Saccharomyces cerevisiae, another marine yeast was utilized by Salunke et al. to biogenerate manganese dioxide nanoparticles.The color of the mixture changed from purple to yellow confirmed the synthesis of MnO 2 NPs which exhibited an absorption peak at 365 nm in the UV-visible spectrophotometry.Further, the FTIR spectrum confirmed the potential secondary metabolites of the yeast, among them proteins and alcoholic compounds to play an effective role in the bioreduction of KMnO 4 to MnO 2 NPs.TEM analysis indicates the presence of uniformly dispersed hexagonal-and spherical-shaped MnO 2 particles with an average size of 34.4 nm (Table 6) [135].

Marine invertebrates
Marine invertebrates are a large group of diverse marine organisms that exist in ocean surface to the ocean floor and into the substrate.They represent 65% of the total living marine organisms.Regarding marine invertebrates morphogenic, maybe simple like soft sac-like animal Cnidaria or complicated such tunicates, the relative genus to vertebrate [136,137].Recently, it was found that around new 709 marine natural products have been identified; 307 of them back to the marine invertebrates and their symbiotic microorganisms [138].The biological diversity of marine invertebrates and their constituents; collagen, phenols, peptides, protein, sterols, glycosides, gangliosides, quinones, terpenoids, macrolides, prostanoids and hydrocarbon derivatives direct us toward employing them in many nanobiotechnological applications [137,139].About 10 mL of an aqueous extract of a marine invertebrate polychaete called Marphysa moribidii was incorporated dropwise into 90 mL of 1 mM AgNO 3 solution.After 24 h. of incubation, the color of the solution had been altered from pinkish to yellowish-brown, indicating the generation of spherical AgNPs with an average size of 40 nm.Compared with crude extract (negative control; p < 0.05), the biosynthesized AgNPs have antibacterial activity against various types of Gram-positive and Gram-negative bacteria employing the disk diffusion method [140].Another study utilized the same species to green fabricate gold nanoparticles.The procedure was carried out at room temperature via mixing 5 mL of polychaete extract solution with 20 mL of gold (III) chloride trihydrate (HAuCl 4 .3H 2 O) 1 mM) in a 100 mL Erlenmeyer flask under stirrer condition (150) rpm for 24 h.Following that, the color started to change from pale yellow to red-ruby and that indicates the reduction of Au 3+ into AuNPs (Au + and Au 0 ) which constructed a SPR band in the range of 520 to 560 nm at UV-Vis spectrophotometric photogram.Importantly, FTIR indicated the functional groups that contribute to the gold salt bioreduction, capping and stabilization are carbohydrates, proteins, and polypeptides, the major constituents of the polychaete [141].
Another marine polychaete collected from the sediments of Uppanar estuary, India was employed in the biofabrication of silver nanoparticles.In a 250 mL Erlenmeyer flask, 10 mL of polychaete aqueous filtrate was combined with 90 mL of 1 mM silver nitrate solution to generate dark brown color solution indicating the production of gold nanoparticles.Atomic force microscopy (AFM), SEM, EDS, XRD analysis display the spherical and triangular morphology of polydispersed AgNPs and their size ranged from 40 to 90 nm.FTIR confirmed the occurrence of functional groups among them OH, N -O, C--C, C -N, and C--CH 2 may have an effective role in the synthesis, capping and stabilization of AgNPs.The antimicrobial of resulted AgNPs had been evaluated against five human pathogenic bacteria i.e., Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Vibrio parahaemolyticus via zone inhibition ranging from 8 to 13 mm diameter (Table 7) [142].

Marine animals
Marine animals also have been shown feasible for the green fabrication of nanoparticles.For example, Nemopilema nomurai, a giant jellyfish isolated from the Eastern South Sea of Korea is capable of reducing the gold ions through mixing 1 mL of jellyfish extract at concentration 0.14% to 0.6% with 1 mL of gold (III) chloride trihydrate solution concentrated at 0.5 mM to 4 mM to generate JF-AuNPs of 35.2 nm with spherical and triangular shapes.The cytotoxic (blocking AKT and ERK Fig. 3. Proposed mechanism of anticancer and drug delivery of nanoparticles. N. Yosri et al. activation) and anti-inflammatory (inhibitory effect on iNOS induction) activities of the nanoparticles had been evaluated against different cell lines, among them HeLa, NIH3T3 and Raw 264.7 cell lines [143].
Seahorse (Hippocampus spp.), a dry marine animal organism, is used for eco-friendly biosynthesis of both gold and silver nanoparticles.The amino acids, the major chemical composition of seahorse organisms, were found to be responsible for silver and gold nanoparticles biosynthesis using an aqueous solution of silver nitrate (30 mL, 10 − 4 M) and chloroauric acid (30 mL, 10 − 4 M) respectively under sunlight conditions.UV − vis spectra affirmed the occurrence of the surface plasmon resonance peaks for gold and silver NPs at 450 and 520 nm, respectively.TEM and SEM analysis suggest that the particles are spherical in shape within the size of 20 ± 5 nm for AgNPs and 10 ± 2 nm for AuNPs.Very importantly, the generated particles have the ability to detect toxic metal ions among them (Cu 2+ , Cr 3+ , V 4+ , and UO 22+ ) [144].
On the other hand, Ren et al. could use a polysaccharide-protein complex isolated from Abalone viscera, a marine organism for biosynthesis and capping selenium nanoparticles.Formation of intermolecular hydrogen and covalent bonds between Se with O and Se with N, allowing the SeNPs to be firmly sealed and capped with the glucosides and peptides of the polysaccharides-protein complex, resulting in excellent dispersion stability in water without any discernible precipitation even after 1 year of storage at 4 • C. PSP-SeNPs, also have an excellent growth-promoting impact on tilapia, whereas PSP-SeNPs supplemented diets of 0.5-4.5 mg/kg for 45 days could increase average final body weight (FBW), weight gain rate (WGR) and specific growth rate (SGR) compared to the control (P < 0.05) [145].
Furthermore, haemocyanin is a natural protein isolated from Penaeus semisulcatu, a green tiger prawn, using a Sephadex G-100 gel filtration column.Nowadays, haemocyanin is employed for the green fabrication of ZnO via applying 5 mL of haemocyanin to 50 mL zinc acetate in distilled water (d.H 2 O) (2 Mm) with stirring for 2 h.resulting in the biogeneration of white fine particles.Ultraviolet-visible (UV-vis) spectrum determined the surface plasmon peak of the synthesized ZnONPs at 350 nm, crystalline nature of ZnONPs reported via XRD analysis.FTIR as well demonstrated the proteins are responsible for the connection between ZnO and haemocyanin.Finally, SEM and TEM confirmed the spherical shape and 10-50 nm size of the synthesized NPs.Notably, these particles at 0-60 mg/kg increase the immunity, feed intake and antioxidant activities of shrimps (Table 8) [146].

Marine sponges
Marine sponges are a large phylum within the animal Kingdom of the genus Suberea (family: Aplysinellidae), characterized as prolific factories for the development of bioactive natural products.This class of compounds show very structural diversity, ranging from basic monomeric molecules to more complicated molecular scaffolds and displaying a myriad of biological, pharmacological and nanotechnology potentialities [147].Very recently, Shady et al. conducted a research to discuss the role of Amphimedon sp., a marine sponge for green synthesis of silver NPs.The sponge was collected from the Red Sea, Sharm El-Shaikh Governorate, Egypt.After the free drying of the sample, 6 g was extracted with methanol-methylene chloride as a crude extract, then fractioned between water and petroleum ether, yielding a petroleum ether fraction.The crude extract and petroleum ether fraction were subsequently used for green synthesis of silver nanoparticles.The size, morphology, nature and metabolite profiling of the resultant particles had been characterized using TEM, UV and FTIR.FTIR is used to affirm the metabolites, among them alkaloids, acids, phenolic and aldehyde compounds, that contribute for silver nanoparticles generation, stabilization and capping.Additionally, these particles have antiviral activity against HCV virus via inhibition of NS3 helicase and NS3 protease [29].
Acanthella elongate, another vital sponge utilized by Inbakandan et al. to biosynthesize gold nanoparticles.The gold NPs were prepared by adding 10 mL of an aqueous solution for the sponge extract to 100 mL of HAuCl 4 (10 − 3 M) aqueous solution.Due to the mixed color adjusted to pinkish ruby red and the occurrence of a UV peak at 526 nm, the production of gold NPs has been confirmed.TEM and XRD also assessed the monodispersed and spherical shapes of the prepared AuNPs with size ranges from 7 to 20 nm.FTIR suggested the amino groups responsible for the biosynthesis and capping of the prepared gold NPs (Table 9) [148].Similarly, Inbakandan et al. used the same species of the sponge for biofabrication of silver nanoparticles by incubation 10 mL of sponge aqueous extract with 100 mL silver nitrate aqueous extract for 2 h.under stirring condition, subsequently, the color changed to yellowish-brown, producing a plasmon band at a UV-visible spectrum of 426 nm.With the help of the TEM image, the silver NPs illustrated as polydispersed spherical shapes with variable diameters ranging from 15 nm to 34 nm [149].
Inbakandan et al. also investigated the ultrasonic-assisted green synthesis of silver nanoparticles employed a marine sponge, Haliclona exigua.The bioengineered nanoparticles exhibited a flower-like shape within the size of 100-120 nm.The amine groups of the sponge chemical composition played a role in biosynthesis and capping of AgNPs.The in vitro anticancer and antibacterial activity of the nanoparticles against wide of microbes and cancer cells had been evaluated as well [150].

Antimicrobial activities
Microbial infections are considered one of the most severe sources of chronic diseases and cause several mortalities worldwide.For a long time, antibiotics have long been the preferred therapy for microbial infections owing to their effective treatment and low cost, but excessive usage of the antibiotics has led to the emergence of multidrug-resistant microbial strains [151].Since multidrug-resistant microbes have become a serious global health threat, there is an urgent need for novel and effective strategies for microbial diseases therapy [152].Consequently, various nanosystems including biogenic/green metallic nanoparticles (NPs) i.e., silver, gold, copper, zinc, and iron oxide, etc. with antimicrobial properties have been extensively studied against multidrug resistance microorganisms separately and/or in synergy modules with the current/conventional antibiotics [153,154].
On the other hand, several studies indicate that silver has proven to be an effective antimicrobial agent as either ionic or colloidal particles.The silver ions are very highly effective as they can bind with protein tissues and that leads to distortion of the bacterial cell wall and nuclear membrane.They can also bind to DNA and RNA via denaturation, causing bacterial replication inhibition to end with the death of the bacterial cells (Fig. 2) [65].To date, several studies have been conducted on the green fabrication of silver nanoparticles (AgNPs) with antimicrobial characteristics using marine organisms.For instance., metallic AgNPs were green synthesized using extracellular extract of marine mangrove (R. mucronate) in combination with antifungal drugs including fluconazole and itraconazole showed high antifungal activity (increase in inhibition zone and fold area) against human fungal pathogens among them C. albicans (MTCC-8123) (12:26 mm; 3.69%), A. fumigatus (MTCC-9657) (16:20 mm; 0.56%), A. flavus (MTCC-277) (13:14 mm; 0.15%) and C. neoformans (MTCC-1346) (13:14 mm; 0.15%) compared to the antifungal drugs individually using disk diffusion assay as listed in Table 1 [33].Moreover, Red Sea sponge (Amphimedon sp.) facilitated green routed AgNPs have also been reported to have antiviral potential against Hepatitis C virus (HCV); the total methanol-methylene chloride extract and petroleum ether fraction of the sponge show inhibition activity against NS3 helicase and protease at IC 50 of 1.52 ± 1.18, 9.76 ± 0.58, 0.11 ± 0.62, and 2.38 ± 0.57 μg/mL (Table 2) [29].
Stable AgNPs synthesized through bioreduction of silver nitrate using marine microalgae T. erythraeum as well show antibacterial potential against drug-resistant pathogenic bacteria including E. coli (Amikacin R ), S. aureus (Tetracycline R ) and S. pneumoniae (Penicillin R ).
The AgNPs at 100 μg/mL show inhibition zones of 10.6 ± 0.65, 15.2 ± 0.33, and 18.5 ± 0.74 mm [41].As well, the inhibition zones of multidrug-resistant bacteria namely, E. coli and B. cereus caused by marine cyanobacterium Oscillatoria limnetica mediated AgNPs were determined to be 22 mm against E. coli and 20 mm against B. cereus using the disc-diffusion method, while standard drugs including cefaxone and tetracycline display inhibition zones of 19 and 18 mm, respectively.Notably, it was found that the synergistic effect of cefaxone-conjugated AgNPs resulted in an inhibition zone with a diameter of 26 mm, which is comparable to the effect of tetracyclineconjugated-AgNPs (24 mm) on B. cereus bacterium [91].
Studies on the antibacterial effect of the marine bacterium Streptomyces sp.mediated AgNPs have revealed their inhibitory effects on drugresistant clinical pathogens including E. coli, A. baumannii, Pseudomons aeroginosa, P. mirabilis, E. faecium, S. aureus and multidrug-resistant namely, S. aureus within MIC of 7.81-62.5μg/mL (Table 4) [115].In general, AgNPs are characterized by distinctive properties i.e., smaller particle sizes, diverse shapes, high chemical stability and good conductivity, which could have increased the membrane permeability.AgNPs can also interfere with the sulfur-containing biomolecules in bacterial cell membranes or can strike the genome and respiratory chain and ultimately resulting in the death of bacterial cells.
On the other hand, gold NPs also have antimicrobial properties owing to their biocompatibility, intrinsic physicochemical, good scattering and absorption properties, oxidation resistance and chemical inertness.Using the Kirby-Bauer method, Pei et al. reported that the antibacterial inhibition zones of the marine baitworm Marphysa moribidii idris biosynthesized AuNPs on E. coli, S. typhi, S. aureus and S. epidermidis have been reported to be 20 ± 0.6, 15 ± 0.6, 18 ± 0.9 and 18 ± 0.9 mm, respectively [141].Moreover, the antibacterial action of biosynthesized AuNPs, AgNPs, and AgClNPs employed marine bacterial exopolymers had been assessed toward Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), as well as fungi (Candida albicans) using the broth dilution micro-method and it was found that MIC and MBC values of 11.25-45 μg/mL were obtained [17].Through another investigation, stable and colloidal AuNPs synthesized from novel marine alga called Ecklonia cava displayed excellent antimicrobial capacity against E. coli, B. subtilis, P. aeruginosa, S. aureus, A. niger, A. brasiliensis, A. fumigates and C. albicans (Table 2) [59].

Cancer therapy and drug delivery
Cancer is a major public health problem and the second leading cause of death after cardiovascular diseases.So far, neither an effective therapy nor diagnosis approach for cancer diseases has been approved [155,156].Recent advances in the nanotechnology field, including NPs fabrication and engineering, have led to the development of new therapeutic and diagnostic approaches called nanotheranostics.Recently, cancer nanotheranostics plays a key role in the management of cancer diseases i.e., drug delivery (Fig. 3), drug-release monitoring, imagingguided focal therapy, post-treatment response monitoring, patient stratification and tumor characterization [157].
Marine organisms show great potential in the green fabrication of NPs with anticancer activities.For instance, the cytotoxic potential of AuNPs from giant jellyfish (Nemopilema nomurai) was evaluated against NIH-3T3, Raw 264.7 and HeLa cells employed the MTS assay.The IC 50 values for the three stated cells are 0.2679, 6.6814 and 0.076 mg/mL respectively.The proliferative activity was owned to the suppression of AKT and ERK proteins activation [143].Moreover, marine sponge (Haliclona exigua) mediated flower-like silver nanocolloids have cytotoxic activity against human oral cancer within an IC 50 of 0.6 μg/mL using MTT assay.The increase in cytotoxicity at very low concentrations reveals the possibility of greater intracellular uptake of silver nanocolloids (positively charged surface) due to the non-specific interaction with the negatively charged cell membranes, facilitating the spread of the drug through the cell membrane [150].
Streptomyces atrovirens (a marine bacterium) mediated AgNPs shown to have in vitro cytotoxic activity against human breast cancer cells using MTT assay.Various concentrations of AgNPs from 2 to 50 μg were added to MCF-7 cell lines for 24, 48 and 72 h and NPs at a dose of 44.51 μg were found effective for 24 h [118].Additionally, according to Hamed et al. green AgNPs synthesized using two strains of marine actinomycetes sp., Streptomyces sp.192ANMG and Streptomyces sp.17ANMG had been reported as cytotoxic agents against hepatocellular carcinoma cancerous cells at concentrations of 40.2 and 25.2 μg/mL, respectively [98].Similarly, the in vitro cytotoxicity potential of marine Escherichia coli VM1bacterium mediated AgNPs toward human lung, cervical and normal (Vero) cell lines was evaluated at various concentrations (25-125 μg/mL).The highest cells growth inhibition was recorded against the lung, cervical and Vero cell lines and accounted for (85.36%, 80.54%, and 54.34%, respectively) at a concentration of 125 μg/mL [105].In another study, Bacillus sp.KFU36 (a marine bacterium) synthesized AgNPs were assessed for their anticancer abilities against breast cancer cell line using MTT assay.Results showed that AgNPs treated MCF-7 cells decreased the cell viability by 15% at 50 μg/mL via induction of apoptotic mechanism [104].
Furthermore, bio-extracted AgNPs with marine seaweed Turbinaria ornate demonstrated an effective cytotoxic campaign over the cells of retinoblastoma Y79 using MTT assay with an IC 50 value of 10.5 μg/mL [83].Carrageenan oligosaccharide polymer of marine red is a potential bioreduction agent for the green synthesis of AuNPs.Carrageenan and carrageenan mediated AuNPs show anti-proliferative potential against various cancerous cell lines, among them colon, breast and umbilical vein endothelial cells using SRB assay.The IC 50 for the carrageenan and carrageenan mediated AuNPs were recorded as 49.9 ± 1.6 μg/mL and 34.4 ± 1.7 μg/mL against colon cell line meanwhile recorded as 164.2 ± 1.8 μg/mL and 129.2 ± 1.7 μg/mL against breast cell lines [71].
For the first time, a marine bacterium called Streptomyces sp. was used for the biosynthesis of novel fucoidanase.The fucoidanase was then used for the green fabrication of AuNPs.Subsequently, the cytotoxicity of fucoidanase-AuNPs toward HeLa cells at different concentrations (50-500 μg/mL) was evaluated for 24 and 48 h.using MTT assay.AuNPs could produce reactive oxygen species (ROS), induce DNA damage and apoptosis in cancer cells with an IC 50 of 350 μg/mL at 24 h.and 250 μg/ mL at 48 h.[101].In another study, fucoidanase-AuNPs could be utilized for doxorubicin drug delivery.A specific amount of doxorubicin was employed for AuNPs dispersion, resulting in a fixed doxorubicin concentration of 10 − 4 M in solution.It was found that the doxorubicin drug release in an acidic medium (pH, 4.5) was greater than in a natural medium (pH 7.4).Fucoidanase, fucoidanase-AuNPs, doxorubicin, and doxorubicin-fucoidanase-AuNPs were evaluated for the first time against human breast cancer cells (MDA-MB-231) and displayed IC 50 35, 30, 15, and 5 μg/mL in 24 h.respectively.DOX-Fu AuNPs could also be used as photoacoustic imaging agents as well [26].
Cobalt oxide (Co 3 O 4 NPs) NPs, other metallic nanoparticles, have also attracted attention in the field of nanobiotechnology owing to their strong electrical potential, super capacitance, ecological nature in addition to their magnetic semiconducting properties, which make cellular uptake fast.Such fast cellular uptake is an effective pathway for cancer therapy.In this context, Co 3 O 4 NPs could be synthesized utilizing marine red algae extract.These particles display anticancer activities against liver cancer with an IC 50 41.4μg/mL.They generate ROS, which induces cellular oxidative stress, causing DNA damage and cell death.In other words, the small NPs could easily penetrate the cell membrane and subsequently destroy the cell barrier and its functionality [72].Ali et al. tested the cytotoxic activity of Ruthenium-NPs (RuNPs) mediated Dictyota dichotoma marine algae against Hela cells.The dose-dependent cytotoxic effect of RuNPs was reported on HeLa cells after incubation with these particles with an IC 50 value 1.56 μg/mL [58].
Taken together, the synthesized NPs have been documented as good anticancer and cytotoxic agents owing to their ability to produce free radicals (reactive oxygen species).The increment and accumulation of ROS cause oxidative stress, resulting in partial or permanent damage of protein integrity and functionality, which causes cellular damage, leading to the death of cancer cells (Fig. 3).Meanwhile, other studies have shown that AgNPs can control the DNA-dependent kinase function, which involves repairing damaged DNA [91].

Antioxidants
Antioxidants could be defined as substances that inhibit the oxidation of the natural compounds by neutralizing the free radicals or scavenging reactive oxygen species (ROS) within the cells [158].In this context, nanomaterials, including NPs are one of the most pioneering frontiers in the field of biomedical sciences i.e., antioxidants.For example, NPs of organic materials and polymers (melanin, lignin), metallic oxides (cerium oxide, Co 3 O 4 ) and metals (silver, gold, platinum) display inherent bio-redox effects [159].
Recently, the antioxidant action of bio-extracted marine red algae mediated cobalt oxide nanoparticles (Co 3 O 4 NPs) was evaluated using1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay.Different concentrations of Co 3 O 4 NPs ranging from (1-200 μg/mL) were applied to 170 μL of DPPH solution in the dark conditions.After 25 min of incubation, the solution was analyzed using a spectrophotometer to determine the radical scavenger activity and the absorbance peak was recorded at 517 nm.The minimum radical DPPH scavenging (37.0%) was recorded at 62.5 mg/mL, while the maximum one (78.1%)was recorded at 500 mg/mL.In this study, Co 3 O 4 NPs are interfered to be electron donors agent, interacting with free radicals to render them into more stable conditions [72].Furthermore, selenium nanoparticles (SeNPs) were biosynthesized by a new marine bacterium Bacillus sp.MSh-1, investigated for DPPH scavenging activity and reducing power assay for the reduction of Fe 3+ to Fe 2+ .It was reported that at a concentration of 200 μg/mL, SeNPs exhibited 23.1 ± 3.4% DPPH scavenging activity [102].
Similarly, marine seaweed Acanthophora spicifera mediated gold nanoparticles were tested on DPPH and nitric oxide (NO 2 ) free radicals.Regarding DPPH, 1 mL of (seaweed extracted-AuNPs) was incubated with 1 mL of DPPH (0.1 mM) for 30 min, while in the case of NO 2 , 10 mM of the sodium nitroprusside solution was mixed with different concentrations (100-500 μg/mL) of AuNPs at 25 • C for 150 min.The absorbance peaks were observed at 546 nm and 540 nm for DPPH and NO 2 respectively.At 500 μg/mL, the AuNPs show the highest DPPH and NO 2 radicals inhibition activity of 62.8% and 59.2% respectively while in the case of the seaweed crude extract, the highest DPPH and NO 2 radicals recorded of 42.2% and 39.8% scavenging activity [50].
Additionally, AuNPs synthesized using marine alga (Gelidiella acerosa), were investigated for in vitro antioxidant activity by DPPH and ferric ion reducing power (FRAP) radical scavenging assays.In the experiment, 1 mL of 0.1 mM DPPH solution was incubated with 2 mL of AuNPs at different concentrations (1-5 μg/mL) for 30 min.and for the FRAP assay, 500 μL of different concentrations of AuNPs (1-5 μg/mL) reacted with 4 mL of ferric chloride hexahydrate solution for 30 min.

Bioremediation (biocatalytic)
Bioremediation is a natural biotechnology process that uses living organisms to degrade toxic waste, and recover the contaminated environments, among them soil and water [160].Nowadays, nanotechnology serves as a brilliant procedure to get off, remove and recycle the contamination caused by various industrial wastes [22].In this context, Edison et al. conducted an experiment using an aqueous extract of marine alga Caulerpa racemose as a reducing agent for AgNPs green synthesis.The biosynthesized AgNPs were observed to be an effective reactant for degradation of methylene blue (MB) dye after 30 min of incubation.AgNPs able to fully degrade the methylene blue dye in the presence of NaBH 4 as a catalyst [43].In a similar study, the marine alga C. serrulate intervened combination of stable AgNPs can be employed to bioremediate Congo red (CR) dye in the presence of NaBH 4 .Briefly, 3 mL of NaBH 4 solution (1.74 mM) was well-mixed with CR aqueous solution (0.067 mM) and a fixed volume of AgNPs to give a total volume of 10 mL.The color of the azo dye didn't change in the presence of only NaBH 4 , but after applying the silver nanoparticles to the reaction medium, the color of the dye started to disappear within 5 min [42].
Padina tetrastromatica, a marine macroalga was utilized by Princy and Gopinath et al. 2018, 2019 to green fabricate AuNPs.The biosynthesized AuNPs were investigated as a catalyst for the biodegradation of 4-nitrophenol (4-NP) to the beneficial 4-aminophenol (AP) and organic dyes i.e., eosin yellow and CR to a colorless solution in the existence of NaBH 4 .Regarding to 4-NP, firstly, 0.3 mL of 2 mM 4-NP and 1 mL of freshly prepared NaBH 4 solutions (0.03 M) were mixed, then 100 μL of biogenic AuNPs (1 mg/mL) were added to the mixed solution.The absorption peaks were recorded at a regular interval using a UV spectrophotometer.Within 4 min, the AuNPs completely degrade 4-NP to 4-AP, as confirmed by the bleaching of yellow color and disappearance of the absorption peak at 400 nm corresponding to 4-NP and appearance of a new peak at 300 nm corresponding to 4-AP.While regarding CR and eosin yellow, complete degradation was totally accomplished after 4 min and 6 min, respectively (Table 2) [69,70].
Through another study, Ramakrishna et al. discussed the role of AgNPs mediated by two marine algae; T. conoides and S. tenerrimum in biocatalysis and degradation of nitro compounds (4-NP and p-nitroaniline), and organic dye molecules (Rhodamine B and Sulforhodamine) in the presence of NaBH 4 (Table 2) [49].The 4-NP dye could also be biodegraded using a marine aquatic plant; Ulva armoricana mediated AuNPs, whereas the biosynthesized AuNPs have the potential to reduce 4-NP to 4-AP with the help of NaBH 4 at a constant degradation rate of 1.49 × 10 − 4 s − 1 [84].Taken together , during the reduction process, NaBH 4 acts as electrons donors (BH 4− ) while the dyes serve as electron receptors and the NPs used as an adsorption surface for the reactant (dyes plus NaBH 4 ).Thus, the nanoparticles proposed to play a key role in the electron transfer process from NaBH 4 (negative charges) to the dyes and accordingly, promote the reduction by reducing the activation energy of the reaction and hence acting as efficient catalyst agents (Fig. 4).
On the other hand, the extracellular polymer of a marine bacterium (Pseudomonas aeruginosa JP-11) mediated CdSNPs could be employed to remove the cadmium pollutants from aqueous solutions.Briefly, 50 mg of the polymer pristine, functionalized polymer and NPs incorporated polymers were individually dispersed with the desired concentration of aqueous cadmium salt aqueous solution (25, 50, 75 and 100 ppm) at an optimum pH and adequate temperature.After 24 h.and 48 h. of incubation, the mixtures were centrifuged to get the metal-ion (Cd 2+ ).Thereafter, atomic absorption spectroscopy (AAS) was employed to determine the concentration of cadmium metal ions using the flame ionization method.The percentage of cadmium removed by the pristine polymer, functionalized polymer and CdSNPs incorporated functionalized polymer were recorded to be 57.41%,61.88%, 77.07%, and 80.81%, 86.46%, 88.66%, respectively at 24 h.and 48 h.[113].

Sensors
Heavy metals such as mercury (Hg), arsenic (As), lead (Pb), nickel (Ni), and cadmium (Cd) are among the most dangerous hazardous materials which cause severe health issues such as cancer, kidney and liver diseases [161].The fast advancement of the nanotechnology field offers the significant motivation of the sensor's performance based on its sensitivity, efficiency, stability, limit of detection, selectivity, and reproducibility [162].In this scenario, a new colorimetric sensor for bisphenol-A detection in the aqueous mediums has been assessed utilizing a marine brown alga (Sargassum boveanum) mediated AgCl-NPs.Briefly, 4 mL of AgCl-NPs was mixed with 0.5 mL of bisphenol-A solutions in deionized or tap water.Subsequently, the color of the solution started to alter from yellow to purple.99% bisphenol-A recovery could N. Yosri et al. be observed with the tap water and the detection limit of the colorimetric sensor is 45 nM [75].Furthermore, in amperometric measurements, marine alga, Sargassum bovinum mediated palladium nanoparticles (PdNPs) were used to detect hydrogen peroxide whereas PdNPs with modified carbon ionic liquid electrode were used as a sensor for detecting H 2 O 2 (5.0 μM-15.0mM) at a sensitivity of 284.35 mAmM − 1 cm − 2 and a detection limit of 1.0 μM [76].
Similarly, mercury metal could be sensitized by employing green synthesized silver-silver chloride nanoparticles (Ag@AgCl-NPs) using an aqueous extract of marine green alga (Chaetomorpha sp).The detection limit of the colorimetric sensor for Ag@AgCl-NPs reported as 4.19 nM.Therefore, the NPs could be potential sensors for detecting mercury in the water [27].Moreover, various ions, among them Cu 2+ , Cr 3+ , V 4+ , and UO 2 2+ could be detected by green synthesized Ag and Au-NPs using the bone powder aqueous extract of a dry marine organism (seahorse) [144].

Discussion
Besides marine organisms, there are other potential sources of products capable of being utilized for the green synthesis of nanostructures (including NPs) such as terrestrial plants, microorganisms (fungi and bacteria), and insects (bees and wasps).However, given that the oceans cover almost 70% of the Earth's surface, marine organisms constitute an extremely broad choice.Furthermore, marine organisms often survive in extreme circumstances, and this confers upon them the ability to produce various chemical constituents that are significantly different in characteristics from those of their terrestrial counterparts.
The literature survey has shown that the noble metals silver and gold are currently most utilized in the biosynthesis of NPs by marine organisms.Algae and bacteria are the most commonly employed aquatic species, exhibiting a good capacity for NP production via eco-friendly biofabrication (Fig. 5).Properties found most prevalently in NPs produced by marine organisms include antibacterial, anticancer, cytotoxic, antioxidant, antifungal, and catalytic properties.
For example, fucoidan and fucoidanase, naturally sulfated polysaccharides isolated from some algae and seaweeds i.e.F. vesiculosus and S. myriocystum and marine bacterium (Streptomyces spp.).To the best of our knowledge, these polysaccharides have not yet been reported from terrestrial plants.These compounds are employed in the biosynthesis of metallic NPs, where the hydroxyl groups of the algal polysaccharides are assumed to be involved in the bioreduction of the metals.Notably, NPs produced using these two compounds show anticancer, antimicrobial, and DOX drug delivery activities.
The antimicrobial action of NPs could be explained by various mechanisms.The death of microbial cells may be due to the interaction between the NPs and the cell membrane, increasing the permeability of the cell wall.NPs may adhere to the sulfur groups of enzymes, resulting in the inhibition of many cellular enzymes, especially those involved in the respiratory chain, leading to protein denaturation.After cell penetration, the NPs may stimulate the generation of reactive oxygen species (ROS) that attack the nucleus and DNA, altering cell signaling pathways and resulting in microbial cell death [42,72].It is suggested that AgNPs show higher antibacterial activity against Gram-negative bacteria than Gram-positive bacteria because the walls of the latter are composed of a thick layer of peptidoglycans that form a rigid structure that resists the penetration of AgNPs [36].
Metallic NPs show potential anticancer and cytotoxic activities through variable mechanisms.For example, Co 3 O 4 and AgNPs have anticancer potential because they can generate ROS that induces cellular oxidative stress and cause breakdown of DNA, protein damage, and cell death [72,91].Furthermore, NPs can cause disruption of the mitochondrial respiratory chain, leading to the production of ROS and interruption of ATP synthesis, resulting in DNA damage [105].
Finally, proteins and polysaccharides are considered the organic components of marine organisms that most often play an effective role in the synthesis of NPs.Polysaccharides have hydroxyl (OH) groups; a hemiacetal reducing end and other functional groups that can play a significant role in the biosynthesis and stabilization of NPs [103].Moreover, it is assumed that proteins can be utilized as reducing, stabilization and capping agents.Proteins can combine with nanoparticles via their free amine groups or cysteine residues, forming a protein covering around AgNPs to prevent agglomeration and thereby stabilize the medium [91].

Conclusion
Despite the fact that 70% of the Earth's surface is covered by the oceans, only a limited number of marine species and/or their metabolites have been discovered to date.Accordingly, only a few marine products have been inspected for their potential in the green synthesis of metallic and nonmetallic NPs.This review has highlighted the potential for eco-friendly NP synthesis using marine organism extracts/polymers, for example, fucoidan, the naturally sulfated polysaccharide that is produced by some aquatic species, among them Fucus vesiculosus seaweed.Fucoidan has been used in the synthesis of AuNPs, which are involved in DOX drug delivery.In addition, three other exopolymers (EPS B3-15, EPS T14 and the poly-γ-glutamic acid γ-PGA-APA) isolated from Bacillus licheniformis, serve as good bioreducing agents in the biosynthesis of Au and Ag nanoparticles that exhibit potent antimicrobial activity.Besides carbohydrates polymers, various proteins from extracts of marine organisms also exhibit good potential for NPs synthesis.It has been suggested that the amino groups of amino acids are responsible for bioreduction and that the carboxylate groups serve as capping and stabilizing agents.Furthermore, species of the soft coral Nephthea are proven promising for biogenic production of AgNPs that exhibit potent anti-inflammatory (anti-COX-2) characteristics.Finally, although further detailed investigations are required to address the most common challenges of nanoparticle and nanocluster fabrication, it is clear that the marine products play a great role in providing a platform for improving various aspects of nanotechnology.

Fig. 1 .
Fig. 1.Schematic diagram of the proposed mechanism of the green synthesis of metallic NPs via marine organisms.

Fig. 4 .
Fig. 4. Proposed mechanisms for degradation and reduction of dyes utilizing silver NPs.

Table 2
Metallic and nonmetallic nanoparticles biosynthesized using algae/derivatives and their applications.

Table 3
Metallic nanoparticles biosynthesized using marine cyanobacteria/derivatives and their applications.

Table 4
Metallic and nonmetallic nanoparticles biosynthesized using marine bacteria/derivatives and their applications.
(continued on next page) N.Yosri et al.

Table 6
Metallic nanoparticles biosynthesized using marine yeasts/derivatives and their applications.

Table 7
Metallic nanoparticles biosynthesized using marine invertebrates/derivatives and their applications.

Table 8
Metallic nanoparticles biosynthesized using marine animals/derivatives and their applications.

Table 9
Metallic nanoparticles biosynthesized using sponges/derivatives and their applications.