Recent Trends in Biomedical Applications of Nanomaterials

Published by Oriental Scientific Publishing Company © 2018 This is an Open Access article licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (https://creativecommons.org/licenses/by-nc-sa/4.0/ ), which permits unrestricted Non Commercial use, distribution and reproduction in any medium, provided the original work is properly cited. Recent Trends in Biomedical Applications of Nanomaterials

There is a growing trend about the design, synthesis and use of engineered nanoparticles (NPs) in different areas including medicine, cosmetics, coating, bioremediation, paints, electronics and food industry (Eswar et (Masserini 2013).Liposomes are used both as an agent in imaging studies as well as drug delivery system, due to their biocompability, biodegradability, low toxicity and the virtue to capsulate both hydrophilic and lipophilic drugs.Important solid core based NPs include gold, silver and iron NPs.Gold nanoparticles (GNPs) possess important physical properties such as surface plasmon resonance and the ability to quench fluorescence (Yeh et al 2012).Dendrimers are a class of NPs that comprise of radially symmetric molecules with homogenous, three-dimensional globular shape and monodisperse structure with branches of atoms (Abbasi et al 2014).Dendrimers have the ability to penetrate the cell wall easily due to their lipophilicity and three-dimensional structure which make them good drug delivery systems.
Carbon nanotubes (CNTs) are hollow materials that can either be a single layer or multiple layers of graphene sheets, named as single walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs) respectively.These nanomaterials possess intrinsic spectroscopic properties that make them efficient for cell tracking and monitoring of targeted drug delivery (Zhang et al 2011).Quantum dots (QDs) range from 2 to 50 nm in size with quantum-confinement property that after excitation can emit fluorescence from visible to infrared regions (Zhang et al 2008).Small sized carbon-QDs have the properties of high conductivity, chemical stability and strong photoluminescence emission than classical QDs (Namdari et al 2017).Graphene oxide (GO) possesses the unique properties of large surface area, hydrophilicity and dispersibility in aqueous solutions and therefore is commonly used for biomedical applications (Sun et al 2014).Nanoparticles possess unique properties that are being explored for their biomedical, engineering and industrial applications.The important biomedical applications of NPs are in imaging, drug delivery, theranostic, and biosensors.

Nanoparticles for Imaging
Nanoparticles are being researched as potential contrast agents in computed tomography (CT) (Cormode et al 2014), optical imaging (Kim et al 2004), photoacoustic imaging (Cai et al 2011), magnetic resonance imaging (MRI) and ultrasonography (Wilson and Burns 2010).Gold nanoparticles (GNPs) have unique X-rays attenuation properties which, combined with their easy surface functionalization, makes them ideal candidates for contrast agents.Surface coating of polyethylene glycol (PEG) on GNPs increases their blood retention.Conjugated with a cancer-specific antibody, PEGylated GNPs have been used for CT imaging in tumor-bearing mice (Nakagawa et al 2016).For CT imaging of a tumor model, small sized polyamidoamine-entrapped GNPs were more easily internalized via endocytosis in the liver, leading to more obvious enhanced contrast (Wang et al 2016).Aziz et al (2017) observed that porous GNPs exhibited higher contrast than solid GNPs for direct CT scanning.For accurate localization and evaluation of atherosclerotic plaques via dualmodal imaging, GNPs were caped with a thin amino-PEGs cover and conjugated with Annexin V and radionuclide Tc-99m simultaneously to form single photon emission imaging probe targeting apoptotic macrophages (Li et    Although NPs are being largely tested for targeted drug delivery in cancer however they may also offer applications in many other disorders such as neurodegenerative, inflammatory and ocular diseases.Functionalized SWCNT restored normal autophagy by reversing abnormal activation of mTOR signaling and deficits in lysosomal proteolysis, thereby facilitating elimination of autophagic substrates in primary glial cells, suggesting SWCNT as a novel neuroprotective approach to Alzheimer's disease (

Nanoparticles for Theranostic Applications
Nanoparticles can also be designed with dual capabilities of both diagnostic and therapeutic applications; this combined property is called 'theranostic'.Nanotechnology has enabled the design and synthesis of smart theranostic NPs that can simultaneously diagnose disease, start treatment, and monitor response (Sneider et al 2017).The advancements in remotely triggered nanotheranostics, using different modes of activators such as photodynamic, photothermal, phototriggered chemotherapeutic release, ultrasound, electrothermal, magnetothermal, X-ray, and radiofrequency has significantly overcome the challenges for successful clinical implementation of this technology (Sneider et al 2017).
Despite the fact that first-generation superparamagnetic iron oxide (SPIO) NPs only had diagnostic capabilities, the new generation SPIO NPs have theranostic applications in image-guided cancer therapies.Polymer-coated theranostic SPIO NPs possess good biocompatibility, biodegradability and versatile functionality rendered by polymeric matrices (Li et al 2017a).Chen et al (2017) developed a dual-modality MRI and near-infrared fluorescence (NIRF) probe comprised of SPIO NPs coated with liposomes to which a tumor-targeted agent (RGD peptide), and a NIRF dye (indocyanine green) were conjugated.This novel dual modality probe showed promising results for accurate tumor detection and resection in a mouse model (Fig. 2).
Wang et al (2017c) constructed poly(lactic-co-glycolic acid) (PLGA) NPs and loaded them with gold nano-rods (AuNRs) and docetaxel (DTX) and finally coated with ultrathin nanofilms of manganese dioxide (MnO2), offering a unique potential for MR imaging, chemotherapy and RF hyperthermia.Hong et al (2017) reported indocyanine green (ICG)-loaded hollow mesoporous silica NPs that behaved nonfluorescent and nonphototoxic extracellularly but after entering the cancer cells, they become highly fluorescent and phototoxic resulting in an enhanced phototherapy of cancer.Kang et al (2017b) developed a nanocarrier, carbon dot (CD) created mesoporous hollow organosilica (C-hMOS) NPs, to deliver anticancer drug and to perform optical imaging.The DOX-caryying C-hMOS efficiently targeted the cancer cells and induced cellular apoptosis in addition to multi-color visualization.The incorporation of CDs with liposome opens up their application in fluorescence cell imaging studies, which is very well supported with fluorescence microscopic analysis of the liposome skin penetration.These nano-liposomes do not show any cytotoxicity for MCF-7 cells; however, when loaded with drug, they are able to destroy the cancer cells with a high rate (Patra et al 2016).Chen et al (2015) developed 131 I-labeled PEG-coated reduced nano-graphene oxide ( 131 I-RGO-PEG) for nuclear imaging guided combined radiotherapy and photothermal therapy that effectively reduced tumors in an animal model.
Khatun et al (2015) synthesized a nanogel using the combination of light-responsive graphene, chemo-agent doxorubicin and pHsensitive disulfide-bond linked HA that exerts an activity with multiple effects: thermo and chemotherapeutic, real-time noninvasive imaging, and light-glutathione-responsive controlled drug release.After injection in tumor bearing mice, there was a significant increase in fluorescence intensity in the tumors after laser irradiation and the tumors showed rapid regression and their size was reduced about 30-fold as compared to controls (Fig. 3).Kang et al (2017a) developed a theranostic system, fibrin-targeted imaging and antithrombotic nanomedicine (FTIAN), for imaging of obstructed vessels and inhibition of thrombus formation.In a mouse model of carotid thrombosis, FTIAN specifically targeted the obstructive thrombus and significantly enhanced the fluorescence/ photoacoustic signal.FTIAN also remarkably suppressed the thrombus formation when loaded with antiplatelet drug tirofiban, suggesting its translational potential for the diagnosis and treatment of obstructive thrombosis (Kang et al 2017a).

CoNClusIoN
Recent researches have shown the enormous potentials of various NPs in the diagnosis and treatment of human diseases.Specific functionalization of NPs render them excellent properties for their applications in contrast imaging, cellular tracking, and image-guided interventions.The new generation nanomaterials have the potential of dual and triple mode imaging for the diagnosis of various diseases including cancer, cardiovascular and brain disorders.Targeted drug delivery is yet another important biomedical application of NPs.By encapsulating drugs inside a nanocarrier, the solubility and stability of drugs can be improved in terms of favorable pharmacokinetics and minimal toxicity.The emergence of theranostic NPs offers an opportunity of using a single agent for disease diagnosis as well as therapy.

ReFeReNCes
al 2014, Kang et al 2015, Khatun et al 2015, Zehedina et al 2015, Nafiujjaman et al 2015, Nurunnabi et al 2015, Nafiujjaman et al 2017).Different types of nanoparticles have been formulated and currently in use for biomedical applications.Nanospheres and nanocapsules are widely used as nanoparticles due to their unique properties such as biocompatibility and bio-mimetic character.Liposomes and micelles are lipid based nanoparticles and are made of an aqueous core and one or more concentric phospholipid bilayers

Fig. 1 .
Fig. 1.Fluorescence images of tumors containing dextran-coated luminescent porous silicon nanoparticles (D-LPSiNPs).(a) Fluorescence images of D-LPSiNPs as a function of concentration using different excitation filters.(b) Representative fluorescence images of a tumor bearing mouse.(c) Ex vivo fluorescence images of tumor and muscle around the tumor from the mouse.(d) Fluorescence images of a tumor slice from the mouse.Red and blue colors indicate D-LPSiNPs and cell nuclei, respectively.The scale bar is 100 µm.Reprinted from Park et al (2009) with permission from Nature Publishing Group

Fig. 2 .
Fig. 2. Theranostic imaging in the orthotopic liver tumor models.(A) The MRI image before SPIO@Liposome-ICG-RGDs injection.(B)The MRI signal is obviously decreased in normal liver tissue after targeted probe injection.(C) Surgical guidance by intraoperative FMI-NIR (fluorescence molecular imaging system).(D) The implanted liver tumor tissue (blue arrow) exhibits obvious contrast in color and texture with normal liver tissues.(E) The merge image of color and fluorescence demonstrates the excellent contrast.(F) The residual tumor node (blue arrow) after the first operation.(G) The residual tumor node exhibits obvious contrast in color and texture with normal liver tissues.(H) The merged color and fluorescence image demonstrates the excellent contrast in the residual tumor node.(I) Identification of the residual tumor after the initial resection.(J) Prussian blue staining confirmation of the targeting ability of SPIO@Liposome-ICG-RGDs. (K) H&E staining confirmation of the liver tumor tissue.Reprinted from Chen et al (2017) under Creative Commons Attribution License Xue et al 2014).Intracerebroventricular injection of microRNA (miR-124) NPs increased the number of new neurons in the olfactory bulb and improved the motor function in 6-hydroxidopamine lesioned mice, a model for Parkinson's disease (Saraiva et al 2016).McMasters et al (2017) reported a hollow NP thermosensitive system as an excellent platform

Fig. 3 .
Fig. 3.In vivo optical imaging and thermo-chemotherapy using the nanogel.(a) Optical imaging of healthy mice.(b) Optical imaging of tumor bearing mice.(c) Light responsive imaging in mice treated with nanogels and laser.(d) Ex vivo imaging and fluorescence intensities of tumors and normal tissues.Organs were arranged in the following order: tumor (T), kidney (K), heart (H), spleen (S), liver (Li), and lung (Lu).(e) Thermo-chemotherapy after treating doxorubicin and the nanogels with and without laser irradiation.(f ) Body weight changes of mice after treatment with the nanogels.Reprinted from Khatun et al (2015) with permission from The Royal Society of Chemistry