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Review

Aptamer-Functionalized Nanoparticles in Targeted Delivery and Cancer Therapy

by
Zhaoying Fu
1,* and
Jim Xiang
2,*
1
Institute of Molecular Biology and Immunology, College of Medicine, Yanan University, Yanan 716000, China
2
Division of Oncology, University of Saskatchewan, Saskatoon, SK S7N 4H4, Canada
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(23), 9123; https://doi.org/10.3390/ijms21239123
Submission received: 20 October 2020 / Revised: 10 November 2020 / Accepted: 11 November 2020 / Published: 30 November 2020
(This article belongs to the Section Biochemistry)
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Abstract

:
Using nanoparticles to carry and delivery anticancer drugs holds much promise in cancer therapy, but nanoparticles per se are lacking specificity. Active targeting, that is, using specific ligands to functionalize nanoparticles, is attracting much attention in recent years. Aptamers, with their several favorable features like high specificity and affinity, small size, very low immunogenicity, relatively low cost for production, and easiness to store, are one of the best candidates for the specific ligands of nanoparticle functionalization. This review discusses the benefits and challenges of using aptamers to functionalize nanoparticles for active targeting and especially presents nearly all of the published works that address the topic of using aptamers to functionalize nanoparticles for targeted drug delivery and cancer therapy.

1. Introduction

The ideal cancer therapeutics should be capable of exerting maximum destruction on cancer cells while being able to keep damage to healthy tissues at a minimum. Many anticancer drugs are toxic to cancer cells and healthy cells largely non-differentially, and the major reason that they cause more damage to cancer is because the cancer cells grow/divide more quickly. Besides, most anticancer drugs are in general evenly distributed throughout the body when administered systemically and the result is that only a very small fraction of the drugs reach the diseased site. Therefore, it is not surprising that selective delivery of anticancer drugs to cancer cells has long been a vigorous pursuit of cancer scientists.
Nanoparticles have the potential to encapsulate and transport anticancer drugs to tumor tissue more effectively [1]. However, nanoparticles per se do not have specificity to cancer cells; the fact that nanoparticles accumulate preferentially in cancer sites is basically due to the enhanced permeability and retention (EPR) effect of the tumor tissue [2]. On the other hand, if nanoparticles could be functionalized by ligands capable of recognizing cancer cells specifically, they will be able to target and deliver cargoes selectively to cancer cells and thus greatly increase the therapeutic index (increasing therapeutic efficacy while reducing toxicity). To date, a number of moieties have been studied to functionalize nanoparticles for specific targeting and aptamer is one of them [3].
This paper discusses aptamer-functionalized nanoparticles in targeted delivery for cancer therapy. It first compares passive and active targeting of nanoparticles, then describes the advantages of using aptamers to functionalize nanoparticles for active targeting, explains the strategies to conjugate aptamers to nanoparticles, and summarizes nearly all of the existing aptamer-functionalized nanoparticles used thus far to study targeted delivery to cancer cells. It finally briefly discusses the challenges facing active targeting.

2. Passive vs. Active Targeting of Nanoparticles

Passive targeting of nanoparticles refers to the passive accumulation of nanoparticles in the tumor tissue, which is generally attributed to the enhanced permeability and retention effect. The concept of EPR was first introduced more than 30 years ago when Maeda and colleagues found that certain macromolecules accumulate preferentially in the tumor tissue [4]. EPR is mainly the result of leakiness of the discontinuous endothelium of angiogenic tumor vasculature combined with defective lymphatic drainage of the tumor matrix, which facilitates the extravasation and accumulation of nanoparticles in tumor. It has been shown that the number of nanoparticles accumulated in tumor tissue may be 10–200 times higher than in normal tissue as a result of EPR. The EPR effect is considered to be the primary element to improve the efficacy and safety of nanotherapeutics. In fact, most of the nanomedicines marketed thus far base their increased therapeutic index mainly on the EPR effect [5].
Nevertheless, the EPR effect alone is insufficient for adequate nanoparticle accumulation, particularly in some circumstances. The EPR effect is not effective for some cancers because of tumor heterogeneity and cancer stage, is even not applicable to some types of cancers, and it is not effective in some patients because of individual differences. A survey of the literature in this area from 2005 to 2015 that included 232 data sets showed that only a median of 0.7% of the systemically administered nanoparticle dose could reach the solid tumor in mouse models [6]; multivariate analysis of the pertinent parameters indicated that tumor type, tumor model, and nanomaterial properties are the major factors to affect the delivery efficiency of the nanoparticles. Research also found that the high interstitial fluid pressure of tumor tissue impedes the extravasation of nanoparticles [7]; some particles that have entered the tumor intercellular space via EPR effect may be forced back into the blood circulation because of the high fluid pressure within the tumor interstitium. It is manifest that blood cancers, very early stage tumors, and small metastasized cancers do not have or have only insignificant EPR effect. In addition, because of tumor heterogeneity, the EPR effect is very poor or not shown in some types of cancers and even in different regions of the same tumor [8]. Clinical observations have also indicated that the EPR effect exhibits significant individual variations among patients; the nanomedicines do not increase the therapeutic efficacy in some subpopulations of the patients [9]. Finally, and most importantly, it is now reckoned that the EPR effect chiefly works in animal models rather than in humans [10]; in patients, their effects are just uncertain (because of interpatient variability); these uncertainties pose the most serious challenge to the rationale of nanomedicine development based on the EPR effect and to the clinical translation of the nanotherapeutics. All the above problems warrant the development of a more effective way to deliver nanoparticles to the site of interest.
Active targeting, which is achieved by conjugating tumor specific ligands to the surface of nanoparticles, can provide a means to complement the EPR effect or solve the aforementioned problems. Common classes of targeting ligands that can functionalize nanoparticles include antibodies or antibody fragments, aptamers, carbohydrates, human transferrin protein, peptides, and vitamins such as folate, etc. Representative tumor biomarkers that can be recognized by the targeting ligands include epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM), human epidermal growth factor receptor 2 (HER2), Mucin-1 (MUC1), nucleolin, platelet-derived growth factor receptor β (PGFRβ), prostate specific membrane antigen (PSMA), transferrin receptor, folate receptor, and so on.
The foremost advantage of actively targeted nanoparticles over passively targeted nanoparticles is that they can add on to or improve the EPR effect. An actively targeted nanoparticle can first enter the tumor tissue via the EPR effect and then target cancer cells through specific ligand recognition of the tumor biomarker. In addition, active targeting can augment the EPR effect by having more particles entering than leaving the tumor interstitium because the particles that already enter stick to the cancer cells and thus lower the concentration of the free nanoparticles in the interstitial space. Studies have already demonstrated that actively targeted nanoparticles tend to accumulate more efficiently in the tumor tissue through their selective binding to receptors on the cancer cells when they enter the tumor interstitium [11].
The ligand-mediated active targeting not only helps nanoparticles selectively reach the tumor; it may also promote cellular internalization of the nanoparticles through receptor-mediated endocytosis since some receptors have the intrinsic property to internalize when bound by a ligand. The importance of cellular internalization should be obvious when we think of the fact that most anticancer drugs exert their actions inside cancer cells. Although nanoparticles themselves can get into the cell through clathirin-mediated endocytosis or fluid-phase pinocytosis, conjugation of active ligands to them may boost the process. Receptor-mediated engulfment has already been observed in many specific ligand conjugated nanoparticles; typical examples of aptamer-mediated cellular internalization include the PSMA-targeting A10 aptamer mediated as well as the nucleolin-targeting AS1411 aptamer mediated internalizations [12,13].
Although the targeting ligands can be conjugated with the anticancer agents such as siRNAs and chemotherapeutics directly, the advantage of using nanoparticles is that they can deliver large amounts of drug payload or diversified therapeutics to cancer cells per delivery and biorecognition event [14]. Having a nanoparticle encapsulate diverse therapeutic ingredients could potentially offer synergistic tumor killing effects (e.g., combining any of these anticancer strategies like chemotherapy, gene silencing, immunotherapy, photodynamic therapy, photothermal therapy, and thermodynamic therapy, etc.). Encapsulating different therapeutics within a nanoparticle may also help to overcome or reduce multiple drug resistance (MDR) because MDR usually does not occur to different drugs at the same time or at the same degree, and the mechanisms of MDR differs with different drugs. One example is that nanoparticle-mediated combination of chemotherapy and photodynamic therapy can overcome drug resistance through invoking multiple anticancer mechanisms including cytotoxicity and significantly enhanced production of reactive oxygen species [15].
Active targeting of nanoparticles could also have additive therapeutic effects by exploiting the drug-carrying and receptor-inhibiting actions at the same time. For instance, anticancer reagent-containing nanoparticles functionalized with HER2-targeting ligand, in addition to delivering the therapeutic ingredients into the target cells can, meanwhile, inhibit the activity of the targeted receptors or remove the receptors from the cell surface by means of internalization [16].

3. Aptamer-Functionalized Nanoparticles in Actively Targeted Drug Delivery

Aptamers are short single-stranded DNA or RNA molecules with defined three-dimensional structures that can selectively bind to target molecules with high affinity [17]. Aptamers are usually produced by selecting them from a large random sequence pool with the technology systematic evolution of ligands by exponential enrichment (SELEX). In addition to their superb binding specificity and affinity, aptamers have a number of other favorable features that together make them very suitable molecules to functionalize nanoparticles for actively targeted delivery. Aptamer functionalized nanoparticles have already demonstrated their effectiveness in targeted delivery of anticancer drugs in numerous preclinical and animal studies, though none of them have as yet entered clinical trial or application.

3.1. The Advantages of Using Aptamers to Functionalize Nanoparticles

Aptamers have a very broad spectrum of target recognition and binding; they have little or no immunogenicity; they can easily be end-attached with a chemical group to conjugate nanoparticles; they are small (only a few nanometers in diameter) and will not increase nanoparticle size significantly after coupling; they are relatively easy to make and to store [17]. Those are the general properties of aptamers that make them one of the best choices to functionalize nanoparticles. Up to now, quite a few aptamers have been used to functionalize nanoparticles for targeted delivery to cancer cells (Table 1).
Apart from the abovementioned characteristics, aptamers have a unique advantage that is related to their production—the establishment of the cell-SELEX technique and its improvements have made the aptamer an especially useful ligand to be used to construct the cancer-targeting nanocarriers (Figure 1).
After the setting up of the prototype SELEX technology in 1990, a selection strategy known as cell-SELEX was developed in 2003 that uses whole (living) cells to select aptamers targeting cell surface molecules [215]. This technique allows for the isolation of cell-recognizing aptamers without prior knowledge of the target molecule(s). In 2006, a negative selection (or counter-selection) process was integrated into the original cell-SELEX strategy, which makes it possible to obtain cell-specific aptamers on researcher’s will [216]. In the new cell-SELEX procedure, the negative selection is performed first, wherein the negative-selection cells (these may be normal cells or any untargeted cells and several different types of cells may be used) are used to absorb the undesired or non-specific aptamers (In this step, the undesired or non-specific oligonucleotides in the pool are removed as they bind to the negative-selection cells). The negative selection is followed by positive selection that is conducted basically in the same way as the conventional cell-SELEX strategy and aims to discard the oligonucleotides that do not bind to the positive-selection cells (usually, certain types of cancer cells or any researcher-intended cells are used for this purpose). Thus, by employing the new cell-SELEX technique, one is able to generate aptamers that can specifically recognize cell surface receptors (or molecules) and thus can effectively differentiate cancer cells from normal cells. More importantly, with certain added steps, the cell-SELEX technique can still select aptamers that not only specifically recognize or target cell surface receptors but also get into the cells through receptor mediated internalization [217].

3.2. Strategies of Conjugating Aptamers to Nanoparticles

Aptamers can be conjugated to nanoparticles directly or indirectly via a linker molecule (a bridge or spacer). Both direct and indirect conjugation can be achieved either covalently or non-covalently (Figure 2).
In covalent conjugation, a functional group (such as a primary amino group or a thiol group) is usually attached to one terminus of the aptamer, which can react with the functional group (such as the carboxylic acid group, the maleimide group, and the aldehyde group) on the surface of the nanoparticle or at one end of the linker molecule, or react with the gold or other metal element or inorganic molecule for inorganic nanoparticles. Common examples of covalent conjugation include the carboxylic acid group and the amino group interaction that results in an amide (or carboxamide) linkage, the carboxylic acid group and the thiol group interaction that results in a thioester bond, the carboxylic acid group and the alcohol group interaction that results in an ester bond, the primary amine group and thiol group interaction that results in a thioamide bond, the thiol group and the thiol group interaction that results in a disulfide bond, and the thiol group and the gold or silver interaction that results in a Au–S or Ag-S bond.
Non-covalent conjugation strategies include high affinity interactions and electrostatic interactions. The former includes avidin–biotin and streptavidin–biotin interactions. The latter are commonly seen when a linker molecule is used, in which case the opposite charges on the linker molecule and on the extended oligonucleotide sequence of the aptamer interact, but also include the using of histidine tags.
Most of the aptamer–nanoparticle conjugates reported thus far utilized the direct and covalent strategy. According to Farokhzad and colleagues [11], “covalently linked bioconjugates may result in enhanced stability in physiological salt and pH whilst avoiding the unnecessary addition of biological components (i.e., streptavidin); thus minimizing immunological reactions and potential toxicity”. Fewer studies used bridge or spacer molecule to link aptamer and nanoparticle together. These are in consideration of avoiding any possible steric or spatial restrictions on aptamer’s binding to target molecule, but an associated problem is the increased size of the conjugates. Several aptamer-nanoparticle constructions, including both direct and indirect linkage, used the avidin–biotin or the streptavidin–biotin system. These interactions are very stable but the bulk of the formulation may increase considerably and potential immunological rejection problems might also result.

3.3. Aptamer-Functionalized Nanoparticles in Pre-Clinical Studies

Up till now, quite a lot of aptamer-conjugated nanoparticles have been developed that can target specific cancer cells, deliver various therapeutic agents into cancer cells, and result in cancer cell toxicity in vitro (e.g., inhibit cell proliferation and induce apoptosis of cultivated cancer cells) and/or anticancer effects in vivo (e.g., inhibit xenograft tumor formation in nude mouse model). An inclusive list of nearly all aptamer-conjugated drug-delivering nanoparticles that have been studied thus far with their characteristics and sources is provided in Table 1. A schematic representation of the action process of aptamer-functionalized nanoparticles acting on a cancer cell is shown in Figure 3.
Farokhzad and Langer et al. [18] first performed the proof of concept study of using the aptamer to functionalize nanoparticles for actively targeted drug delivery in 2004. The authors synthesized the nanoparticles of poly (lactic acid)-block-polyethylene glycol copolymer with a terminal carboxylic acid functional group (PLA-b-PEG-COOH) and encapsulated the nanoparticles with rhodamine-labeled dextran as a model drug; they then covalently attached the PSMA-targeting A10 RNA aptamer to the nanoparticles through the reaction of the amino groups on the 3′ end of the aptamers with the carboxylic acid groups on the surface of the nanoparticles. These aptamer–nanoparticle conjugates were demonstrated to be able to target the PSMA-positive prostate LNCaP cells significantly more efficiently compared with the same PEGylated nanoparticles without aptamer conjugation and could get internalized into the cells. The uptake of these conjugates was not boosted in the PC3 cells that are also prostate-derived but do not express PSMA.
A similar nanoparticle-aptamer construction, which used the same PSMA-targeting aptamer but used poly (lactic-co-glycolic acid)-block-polyethylene glycol copolymer with a terminal carboxylic acid group (PLGA-b-PEG-COOH) as nanomaterial and encapsulated the anticancer drug Docetaxel within the nanoparticles, was later assessed both in vitro and in vivo by the same laboratory. The in vivo results showed that the aptamer-targeted drug-loaded nanoparticles exhibited significantly more reduced toxicity (side effects) in the nude mice as measured by mean body weight loss than non-targeted nanoparticles, and intratumoral injection of these aptamer-targeted drug-loaded nanoparticles resulted in complete tumor reduction in five of seven LNCaP xenograft nude mice compared with two of five for non-targeted nanoparticles [19].
Up to the present time, polymers, which include miscellaneous classes with PLGA-PEG being the most frequently used, remain the most used nanomaterials to construct aptamer functionalized nanoparticles to study targeted delivery for cancer therapy, followed by lipid based materials, particularly liposomes and nucleic acid based nanoparticles, including either DNA or RNA. Other organic nanomaterials that have been used include dendrimers, chitosan, proteins/peptides, or hybrids of the above. There are also many inorganic nanomaterials that have been studied in this area, including gold (Au) compounds, silver (Ag), mesoporous silica, graphene based, Calcium carbonate, ZnO, iron, etc. Other and special inorganic nanomaterials include magnetic nanomaterials, quantum dot based nanoparticles, and so on. In addition, organic and inorganic hybrids have also been used. Refer to Table 2 for a classified list of these nanoparticles and nanomaterials with their payloads, targets, related cancers, etc.

4. Challenges Facing Actively Targeted Delivery

Although active targeting holds much promise, several challenges exist. These include the increased complexity of synthesis and purification, the increased cost to make the conjugants, the alterations of nanoparticle properties, choosing a suitable tumor marker or receptor to target, and so forth.

4.1. Potential Alterations of Nanoparticle and Ligand Properties after Conjugation

Ligand conjugation may alter the properties of the nanoparticle. Not only will it increase nanoparticle size; it can also change the charge and modify the conformation of the nanoparticle. The change of nanoparticle size is likely to affect their pharmacokinetics; the change of nanoparticle charge will probably complicate their cellular uptake; the change of nanoparticle conformation may influence the binding feature of the attached ligand because of inadequate steric freedom or decreased orientation. All these must be taken into consideration in making actively targeting nanoparticles.
Although conjugating ligands to nanoparticles might change the pharmacokinetic property of the nanoparticles, this may not be a problem for aptamer conjugation because aptamers are very small, about 2–3 nm in length, in comparison with the drug-carrying nanoparticles, which is typically around 100 nm or larger in diameter. In fact, no literature has reported any alterations in the pharmacokinetics of nanoparticles following aptamer coupling.
Aptamers are commonly modified before therapeutic use. The purpose of modification is to increase their stability against nuclease degradation or prolong their half-life against kidney filtration. Aptamer modification can be performed during selection or after selection. The former aims at stabilizing the aptamers against nucleases. The latter aims at prolonging renal retention and is frequently done with PEGylation, covalent attachment of PEG to one end of the aptamer. Therefore, the attachment of aptamers to a nanoparticle will favorably increase their stability.
However, conjugation of aptamers to a nanoparticle might interfere with their proper folding and change their binding specificity and affinity. For example, the surface charge of the nanoparticle and the density of the attached aptamers on the nanoparticle may both affect their folding and three-dimensional structure. In addition, aptamers that are coupled directly to a nanoparticle may not recognize and bind their target effectively because there is no sufficient space (stereo-interference effect). Sometimes, the orientation of aptamer immobilization may also affect aptamer binding. All these problems should be considered by the researchers and optimum parameters or corresponding resolving measures be taken. For instance, the density and the orientation of attached aptamers can be investigated and optimized, and when stereo-interference occurs, the researchers can consider the use of a spacer molecule.

4.2. Selection of Suitable Tumor Marker or Receptor

The ideal receptor for targeted therapy is one that is exclusively presented on the tumor cells but not on the healthy cells. However, such a receptor may not exist in reality. What we can do is to choose the receptors that have a higher expression level on tumor cells than on healthy cells. The expression of the target receptors on healthy cells, though at a lower level, still carries a potential risk of off target binding. What is more, binding to these receptors may consume or waste the therapeutic nanoparticles and lower its concentration to reach the tumor.

4.3. The “Binding Site Barrier” Effect

Aside from the challenges mentioned above, there may also be the “binding site barrier” problem, which refers to a situation wherein high affinity binding to target cells prevents in-depth and uniform penetration of the targeted therapeutics into the tumor tissue. This phenomenon was first observed by Weinstein and colleagues [218,219] with antibodies, which showed that (1) antibody–antigen binding in tumor-retarded antibody percolation and (2) high antibody affinity had a tendency to decrease antibody percolation. The explanation to the phenomenon that higher-affinity antibodies penetrate the tumor tissue less efficiently than lower-affinity antibodies is that during tissue penetration, the higher-affinity antibodies bind tightly to the cells they first meet and so there are fewer free antibody molecules available; in contrast, lower-affinity antibodies tend to bypass these target cells and can penetrate deeper. Although the “binding site barrier” was originally demonstrated in antigen–antibody interaction, it may be reasonably extrapolated to the actively targeted nanoparticles and a similar phenomenon has in fact be observed by Miao et al. [220] using anisamide ligand targeted lipid-coated calcium phosphate nanoparticles. Therefore, it is essential to seek a balance between the affinity of active tumor targeting and the depth of nanoparticle penetration; trial and error may be necessary [221].

5. Conclusions

The first nanotechnology-based anticancer medicine was approved by the United States Food and Drug Administration (FDA) in 1996, which used PEGylated liposomes to encapsulate the chemotherapeutic drug doxorubicin. Today, about ten nanoparticle based medications are on the market (approved by FDA or other agencies) for cancer therapy [14,222]. All of them are non-targeted or passively targeted. These nanodrugs could delay the clearance or prolong the half-life of the drugs and reduce side-effects to a certain degree. However, only a modest increase in therapeutic efficacy could be observed and the undesired off-target problem still exists, which calls for the development of active targeting of nanoparticles. At the present time, more than a dozen nanoparticles for cancer therapy are undergoing clinical trials [2], of which several are actively targeted, but none of them are aptamer-functionalized. Actively targeted, especially aptamer-functionalized, nanoparticles hold great promise for future nanodrug development and applications. Therefore, more efforts are needed to further the investigation in this area, to refine the experiments and overcome the obstacles for clinical translation. Some obstacles for developing aptamer conjugated-nanoparticles into clinical use include insufficient data about their off-target effects and toxicity either in animals or in human. Venditto and Szoka once notified in their review paper titled Cancer nanomedicines: so many papers and so few drugs published in 2013 that “if we are truly interested in bringing more drugs into the clinic we should focus less on our publication record and more on devising scientific progress that translates into patient treatment” [223]. The same situation exists in the investigation of aptamer-functionalized nanoparticles when we take notice of the fact that more than two hundred papers have been published so far but none of the aptamer-functionalized nanoparticles have entered clinical trials, not to mention clinical application.

Funding

This work was supported by NSFC, grant number 81760732.

Conflicts of Interest

The author declares no competing interests.

Abbreviations

3WJ-RNAa highly stable three-way junction (3WJ) motif from phi29 packaging RNA
5-FU5-fluorouracil
ALCLanaplastic large cell lymphoma
ALKanaplastic lymphoma kinase
ALLacute lymphoblastic leukemia, also known as T-cell acute lymphoblastic leukemia
AML-M2acute myeloid leukemia subtype 2
APTES(3-aminopropyl) triethoxysilane
BSAbovine serum albumin
cMethepatocyte growth factor receptor
COOH(terminal) carboxylic acid group
CSCcancer stem cell
CTCcirculating tumor cell
CUR-NPcurcumin-loaded lipid-polymer-lecithin hybrid nanoparticle
Cyt ccytochrome c
DAUdaunorubicin
DGLdendrigraftpoly-L-lysines
DOTAP1,2-dioleoyl-3-trimethylammonium-propane
DNRdaunorubicin
DOXdoxorubicin
dsDNAdouble-stranded DNA
DSPE1,2-distearoyl-sn-glycero-3-phosphoethanolamine
EGFREpidermal growth factor receptor
EHHelectrostatic adsorption, hydrogen bonding, and hydrophobic interaction
Ehrlich’s ACCEhrlich’s ascites carcinoma cell
ELPelastin-like polypeptide
EpCAMepithelial cell adhesion molecule
EPIepirubicin
FGFR1fibroblast growth factor receptor type-1
FMSNfluorescent mesoporous silica nanoparticle
FNfibronectin
FOFerric oxide
FoxM1Forkhead box M1
Gd:SrHapgadolinium-doped luminescent and mesoporous strontium hydroxyapatite
GMNPgold-coated magnetic nanoparticle
GNPgold nanoparticle
GOGraphene oxide
GPNgefitinib-loaded poly (lactic co-glycolic acid) nanoparticle
GQDgraphene quantum dot
GSTglutathione S-transferase
HAHyaluronic acid
HAS-CShuman serum albumin coated with chitosan
HBLLhuman B cell leukemia and lymphoma
HCCHepatocellular carcinoma
HER3human epidermal growth factor receptor 3
Hishexahistidine
HMME is a photosensitizer
HPAheparanase
HPAEGpoly(2-((2-(acryloyloxy)ethyl)disulfanyl)ethyl 4-cyano-4-(((propylthio)carbonothioyl)-thio)-pentanoate-co-poly(ethylene glycol) methacrylate)
HSP71heat shock cognate 71 kDa protein
HTThyperthermia therapy
IL-6Rinterleukin-6 receptor
IONPIron oxide nanoparticle
KG6Eglutamic acid-modified dendritic poly(L-lysine) system
KLA(KLAKLAK)2 peptide
LP-DNAliposome-polycation-DNA
MAAmethacrylamide
MAGEmelanoma-associated peptide antigen
MALmaleimide
MASIN-(methacryloxy)succinimide
MCSMyristylated Chitosan
MMAmethyl methacrylate
MOF(mesoporous) metal-organic framework
MPCmesoporous carbon
MPEGPoly(ethylene glycol) methyl ether
M-PLGAmannitol-functionalized poly(lactide-co-glycolide)
MSNMesoporous silica nanoparticle
mTECmouse tumor endothelial cell
MDRmultiple drug resistance
MUC1Mucin-1
NHSN-hydroxysuccinimide
NIR PLNnear infrared-persistent luminescence nanomaterials
NMOFamino-triphenyl dicarboxylate-bridged Zr4+ metal-organic framework nanoparticle
NPnanoparticle
NSCLCnon-small cell lung cancer
ONToligonucleotide
PAApolyacrylic acid
PAMPeptide amphiphile micelle
PAMAMpolyamidoamine
PBABTpoly (butylene adipate-co-butylene terephthalate)
PCLpoly(ε-capro-lactone)
PDAhydrochloride dopamine
PDGFRplatelet-derived growth factor receptor
PECpolyelectrolyte complexe
PEEUApolyethylenimine-urocanic acid
PEGpolyethylene glycol
PEIpolyethylene imine
PF127Pluronic F127
PFK151-(4-pyridyl)-3-(2-quinoline)-2-propyl-1-one (an aerobic glycolysis inhibitor)
PFOBPerfluorooctylbromide
PGFRβplatelet-derived growth factor receptor β
P-gpP-glycoprotein
PLApoly(lactic acid)
PLGApoly(lactic-co-glycolic acid)
PLK1Polo-Like Kinase 1
PLLpoly (L-lysine)
pPEGMA-PCL-pPEGMApoly(poly(ethylene glycol) methacrylate)-poly(caprolactone)-poly(poly(ethylene glycol) methacrylate)
PTK7protein tyrosine kinase-7
PTTPhotothermal therapy
PVPpoly (N-vinylpyrrolidone)
PβAEpoly (β amino ester)
QDquantum dot
RBCmred blood cell membrane
SATB1special AT-rich sequence binding protein 1
SPIONsuperparamagnetic iron oxide nanoparticles
SPMFNSuperparamagnetic Ferroarabinogalactan Nanoparticles
TAG-72tumor-associated glycoprotein 72
TDthiolated dextran
TiO2titanium dioxide
TLRToll-like receptor TLR4-siRNA
TM-JM1/2transmembrane-juxtamembrane 1/2 domain
TMPyP5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin
TMPyP45,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin
TNBCtriple-negative breast cancer
TPGSD-α-tocopheryl polyethylene glycol 1000 succinate
TSPthermosensitive polymer
UCNPup-conversion luminescent
NaYF4Yb(3+)/Er(3+) nanoparticle
VEGFvascular endothelial growth factor
β-CDβ-cyclodextrin

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Ijms 21 09123 g001 550
Figure 1. Selection procedure of cell-internalizing DNA aptamer using cell-SELEX.
Figure 1. Selection procedure of cell-internalizing DNA aptamer using cell-SELEX.
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Figure 2. Common strategies of nanoparticle-aptamer conjugation.
Figure 2. Common strategies of nanoparticle-aptamer conjugation.
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Figure 3. Schematic representation of aptamer-functionalized nanoparticle acting on a cancer cell.
Figure 3. Schematic representation of aptamer-functionalized nanoparticle acting on a cancer cell.
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Table
Table 1. Aptamer-functionalized nanoparticles designed for actively targeted drug delivery and cancer therapy in laboratory investigation stage.
Table 1. Aptamer-functionalized nanoparticles designed for actively targeted drug delivery and cancer therapy in laboratory investigation stage.
AptamerNanomaterialPayloadConjugationSize (nm)TargetCancer/Cell LineLevelRef.
A10, RNAPLA-PEG-COOH Rho-labeled dextranDirect #, covalent≈264PSMAProstate cancerin vitro[18]
A10, RNAPLGA-PEG-COOH DocetaxelDirect, covalent≈168PSMAProstate cancerin vitro + in vivo[19]
A10, RNAPLGA-PEG-COOHCisplatinDirect, covalent≈155PSMAProstate cancerin vitro[20]
sgc8c, DNAAu-Ag nanorodPhotothermal therapyDirect, thiol linkageNo dataCCRF-CEM cellALLin vitro[21]
A10, RNASPIONDoxorubicinDirect, covalent66.4 ± 1.5PSMALNCaP cell linein vitro[22]
sgc8c, DNAPAMAM dendrimerNoneDirect, covalent≈8CCRF-CEM cellALLin vitro[23]
AS1411, DNALiposomeCisplatinCovalent, to cholesterol≈200NucleolinMCF-7 cellsin vitro[24]
S2.2, DNAPLGA-COOHPaclitaxelCovalent, DNA spacer≈225.3Mucin-1Breast cancerin vitro [25]
AS1411, DNAPEG-PLGAPaclitaxelDirect, covalent156 ± 54.8NucleolinGliomain vitro + in vivo [26]
No name, DNADNA icosahedraDoxorubicinDirect, covalent28.6 ± 5.0Mucin-1MCF-7 cellsin vitro[27]
A9, RNASPIONDoxorubicinONT linker, base pairing65 ± 12PSMALNCaP cell linein vitro + in vivo[28]
A9, RNAONT-PAMAM dendrimerDoxorubicinONT linker, base pairingNo dataPSMAProstate cancerin vitro + in vivo[29]
No name, RNA QD-PMAT-PEIsiRNAChimera with siRNA66.3–76.5PSMAC4–2B cellsin vitro[30]
XEO2mini, RNAHybrid lipid-polymerDocetaxelDirect, covalent50–100PC3 cellsProstate cancerin vitro[31]
AS1411, DNAPLGA-lecithin-PEGPaclitaxelCovalent, to PEG60–110 NucleolinGI-1 and MCF-7 cellsin vitro[32]
AS1411, DNAPLGAPaclitaxelDirect, amide linking ≈200NucleolinGI-1 cellsin vitro[33]
AS1411, DNAPEG-PCLDocetaxel, DiR, coumarin-6Direct, covalent170.6NucleolinbEnd.3 and C6 cellsin vitro + in vivo[34]
AS1411, DNAMesoporous silicaGold nanorods *ONT linker, base pairing ≈60NucleolinMCF-7 cellsin vitro[35]
GMT8, DNAPEG-PCLDocetaxelDirect, covalent111.9 ± 64.2U87 cellsglioblastoma in vitro + in vivo[36]
AS1411, DNAGd:SrHap nanorodDoxorubicinDirect, covalent153NucleolinMCF-7 cellsin vitro[37]
AS1411, DNAMesoporous silicaDoxorubicinElectrostatic binding≈140NucleolinMCF-7 cellsin vitro[38]
AS1411, DNAMesoporous silicaFluoresceinSulfo-GMBS linker190NucleolinMDA-MB-231in vitro[39]
Sgc8, DNAMesoporous silicaDoxorubicinAvidin-biotin interaction≈150PTK7CEM cellsin vitro[40]
AS1411, DNALiposomeDoxorubicinCovalent, to cholesterol≈200NucleolinMCF-7 breast cancer cellsin vitro + in vivo[41]
A10, RNAH40-PLA-PEGDoxorubicinCovalent, to PEG≈69PSMACWR22Rν1 cellsin vitro + in vivo[42]
5TR1, DNASPIONEpirubicinDirect, covalent≈57Mucin-1carcinoma C26 cellsin vitro[43]
No name, RNAHollow gold nanosphereDoxorubicinDirect, thiol–Au bonds≈42CD30Lymphomain vitro[44]
sgc8c, DNAAptamer DNAAntisense ONT to P-gpDirect, covalent218CCRF-CEM cellALLin vitro[45]
Sgc8, DNADNA nanotrainsGold, DOX, DNR, and EPIDirect, covalentNo dataPTK7ALLin vitro + in vivo[46]
No name, DNADextran-ferric oxideNone (HTT)PDPH linker≈70HER2SK-BR3 cellsin vitro[47]
AS1411, DNAPLGA-PEGVinorelbineDirect, covalent<200NucleolinMDA-MB-231 cellsin vitro[48]
No name, DNALiposomeTSPAvidin-biotin interactionNo dataPDGFRBreast cancer cellsin vitro[49]
AS1411, DNAPEGylated liposomeAnti-BRAF siRNAVia PEG linker≈150NucleolinA375 tumor xenograftin vivo[50]
No name, RNAPLGA-lecithin-PEGCurcuminDirect, covalent90 ± 1.9EpCAMHT29 cellsin vitro[51]
AS1411, DNApPEGMA-PCL-pPEGMADoxorubicinDirect, covalent≈140NucleolinMCF-7 and PANC-1 cellsin vitro[52]
AS1411, DNAGold nanoparticleDoxorubicin or AZD8055Dithiolane linkerNo dataNucleolinMCF-7, el202 and OMM1.3 in vitro[53]
A10, RNA and DUP-1PEG-gold nanostarNone (PTT)Direct, di- sulfide bonds61.90 ±1.61Prostate cellProstate cancerin vitro[54]
No name, DNAChitosanSN38Direct, covalent≈200Mucin-1Colon cancer HT-29 cellsin vitro[55]
AS1411, DNAGold nanoparticleDoxorubicin and TMPyP4Tethered by 21 bp DNA38.7 ± 1.4NucleolinHeLa and MCF-7R cellsin vitro[15]
No name, RNALiposomeDoxorubicinTethered by linker DNA90–100PSMALNCaP cellsin vitro + in vivo[56]
No name, DNAGold nanoparticleProteinWith a His-tag83.0 ± 1.3His or GSTHeLa and A431 cellsin vitro + in vivo[57]
A10–3.2, RNAPEG-PAMAMMicroRNADirect, covalent177 ± 17.5PSMAProstate cancerin vitro + in vivo[58]
A10–3.2, RNAAtelocollagenMicroRNADirect, covalent221 ± 6.9PSMAProstate cancerin vivo[59]
AS1411, DNAPF127-β-CD-PEG-PLADoxorubicinCovalent, to PF127≈39.15NucleolinMCF-7 cellsin vitro + in vivo[60]
No name, RNAPLGANutlin-3aDirect, covalent292 ± 10EpCAMZR751, MCF-7, SKOV3in vivo[61]
No name, RNAPLGA-PEGDoxorubicinDirect, amide linking136 ± 0.21EpCAMNon-small cell lung cancerin vitro + in vivo[62]
No name, RNAPEIEpCAM siRNAElectrostatic interaction198 ± 14.2EpCAMMCF-7 and WERI-Rb1 cellsin vivo[63]
HB5, DNAMesoporous silica-carbonDoxorubicinthiol-amine link to PEG≈140HER2SK-BR-3 cellsin vivo[64]
No name, DNAAu–GONone (PTT)Direct, Au–S bondNo dataMucin-1MCF-7 cellsin vivo[65]
sgc8c, DNAGold nanorodHyperthermia therapyDirect, Au–S bondNo dataCCRF-CEM cellALLin vitro[66] *
No name, RNAPEG-PLGADoxorubicinDirect, covalent136 ± 0.21EpCAMMCF-7 cellsin vitro[67]
AS1411, DNAMOF shell, UCNP coreDoxorubicinDirect, covalent≈140NucleolinMCF-7 and 293 cellsin vitro[68]
No name, RNAGPNGefitinibDirect, covalentNo dataEts1H1975 cellsin vitro + in vivo[69]
No name, DNAHyaluronan/Chitosan5-fluorouracilDirect, covalent181Mucin-1Colorectal cancerin vitro[70]
Cy5.5-AS1411GO and MSNDoxorubicinNon-covalentNo dataNucleolinMCF-7 cellsin vitro[71]
A15, RNAPLGA-PEG-COOHSalinomycinDirect, covalent159.8CD133Osteosarcoma CSCsin vitro + in vivo[72]
S2.2, DNAGraphene oxide-goldDoxorubicinThiol–Au bondsNo dataMucin-1A549 and MCF-7 cellsin vitro[73]
A15, CL4; RNAPLGASalinomycinDirect, covalent139.7, 141.9CD133, EGFR Hepatocellular carcinomain vitro + in vivo[74]
S2.2, DNAZnO nanoparticleDoxorubicinAPTES linkage5–10Mucin-1MCF-7 cellsin vitro[75]
SRZ1, DNADOTAP:DOPE liposomeDoxorubicinNo data≈1004T1 cells4T1 cellsin vitro + in vivo[76]
AS1411, DNATocopheryl PEG-PβAEDocetaxelNo data116.3 ± 12.4NucleolinSKOV3 ovarian cancer cellsin vitro[77]
No name, DNAChitosan and HASN38Direct, covalent129 ± 3.2Mucin-1HT29 cellsin vitro[78]
S6, DNADendrimerMicroRNADirect, covalent100–200A549 cellsNSCLC cellsin vitro[79]
AS1411, DNAPLL-alkyl-PEIshRNAelectrostatic coupling168–183NucleolinA549 cellsin vitro[80]
AS1411, DNAGQD-FMSNDoxorubicinDirect, amide bond72.5NucleolinHeLa cellsin vitro[81]
KW16–13, DNAPEG-gold nanorodNone (PTT)Direct, covalentNo dataMCF10CA1h cellHuman breast duct carcinomain vitro[82]
No name, DNAAu-SPIONGold for PTTThiol–Au interaction≈39Mucin-1Colon cancerin vitro[83]
MA3IronNone (HTT)Streptavidin-biotin, direct≈296Mucin-1MCF-7 cellsin vitro[84]
No name, RNAAlbuminCisplatinDirect, amide bond≈40EGFRHela cell linein vitro + in vivo[85]
No name, DNAHuman IgGmiR29bIndirect, C12 spacer595.9 ±43.1Mucin-1A549 cellsin vitro[86]
sgc8c and AS1411GoldDaunorubicinDirect, covalentNo dataALL and nucleolin Molt-4 cellsin vitro[87]
No name, RNAGoldAntisense ONTSpacer, covalent<50CD33, CD34AML-M2in vitro[88]
No name, DNAMesoporous silicaDoxorubicinDirect, covalent181 ± 6EpCAMSW620 colon cancer cellsin vitro[89]
TSA14, RNAPEGylated-liposomeDoxorubicinDirect, covalent118 ± 2.2TUBO cellsBreast cancerin vitro + in vivo[90]
DNA-RNA hybridSPIONDoxorubicinDNA linker, streptavidin-biotinNo dataPSMAProstate cancerin vitro[91]
AS1411, DNAGC-rich dsDNADoxorubicinDirect, covalent6.1 ± 0.7; 7.4 ± 0.4NucleolinDrug-resistant MCF-7 cellsin vitro[92]
AS1411, DNAPEG-PLGAGemcitabineDirect, covalent128 ± 5.23NucleolinA549 cellsin vitro[93]
AS1411, DNAHPAEGDoxorubicinDirect, covalent93.7NucleolinMCF-7 and L929 cellsin vitro[94]
No name, DNADNA dendrimerEpirubicinNo data36.4MUC1, AS1411MCF-7 and C26 cellsin vitro + in vivo[95]
A10, RNAPLGATriplex forming oligonucleotideDirect, covalentNo dataPSMALNCaP cellsin vitro[96]
No name, RNAPLGA-PEGDocetaxelDirect, covalent93.6PSMALNCaP cellsin vitro + in vivo[97]
AS1411, DNAM-PLGA–TPGSDocetaxelDirect, covalent130.1 ± 2.9NucleolinHeLa cellsin vitro + in vivo[98]
Endo28, DNA3WJ-RNADoxorubicinDirect, covalent8.1 ± 1.5Annexin A2Ovarian cancerin vitro + in vivo[99]
No name, DNAHAS-CSPaclitaxelAcrylate spacer170 ± 4Mucin-1MCF-7 and T47D cellsin vitro[100]
AS1411, DNAPEG-PAMAM dendrimer5-fluorouracilCovalent, to PEGNo dataNucleolinGastric cancerin vitro[101]
Two, DNADGL-PEGDoxorubicin ATP-aptamerCovalent, to PEG≈38Nucleolin, Cyt cNucleolin+ HeLa cellsin vitro + in vivo[102]
No name, DNAIron oxideNone (HTT)No dataNo dataFGFR1Human osteosarcomain vitro[103]
A10, RNALiposomeCRISPR-Cas9 plasmidCovalent, to DSPE-PEG≈150PSMAProstate cancerin vitro + in vivo[104]
AS1411, DNAPEG-PAMAM dendrimerCamptothecinCovalent, to PEG≈18NucleolinHT29 and C26 cellsin vitro + in vivo[105]
A6, DNALipid-polymer liposomesiRNADirect, covalent270 ± 10; 237 ± 12HER2SKBR-3 and 4T1-R cellsin vitro[106]
No name, DNAChitosan- liposomeErlotinibDirect, covalent179.4 ± 1.16EGFREGFR-mutated cancer cellsin vitro[107]
AS42, DNAGoldNone (PTT)No data≈37Ehrlich’s ACCEhrlich carcinomain vivo[108]
No name, DNAMCS nanogelDoxorubicinDirect, covalent15–25LNCaP cellProstate cancerin vitro[109]
AS1411 + S2.2, DNAGold-coated liposomeDocetaxelthrough S-Au bond≈200Mucin-1, NucleolinMCF-7 cellsin vitro + in vivo[110]
5TR1, DNAPLGA-chitosanEpirubicinElectrostatic coupling≈222.7Mucin-1MCF-7 and C26 cellsin vitro + in vivo[111]
AS1411, DNAAlkyl PAMAM dendrimerBcl-xL shRNACovalent and non-covalent148–230NucleolinA549 cellsin vitro[112]
Gint4.TPLGA-PEG-COOHPI3K-mTOR inhibitorDirect, covalent52 ± 1PGFRβGlioblastoma U87MG cellsin vitro + in vivo[113]
No name, DNAMesoporous silicaEpirubicinVia disulfide bonding258.5 ± 20.1Mucin-1MCF-7 cellsin vitro[114]
No name, DNAAminopropyl MSNSafranin Oelectrostatic + H-bonding≈407Mucin-1MDA-MB-231 cellsin vitro[115]
No name, DNAChitosan- liposomePFOB and ErlotinibDirect, covalent≈180EGFRNSCLC cell linesin vitro + in vivo[116]
No name, DNAAu-Fe3O4NoneElectrostatic absorption46 ± 3VEGFSKOV-3 ovarian cancer cellsin vitro[117]
No name, DNAMPC-PAA/PEIDoxorubicinAnchoring via EHH No dataMucin-1A549 and MCF-7 cellsin vitro[118]
A15, RNAPLGAPropranololDirect, covalent143.7± 24.6CD133Hemangiomain vitro + in vivo[119]
AIR-3A, RNAPEG-coated gold NPNoneThiol–gold bonds2, 7, 36IL-6RIL-6R-carrying cellsin vitro[120]
No name, DNAPDA/PEG- coated MSNDM1Direct, covalent203.75 ±2.37EpCAMColorectal cancerin vitro + in vivo[121]
AS-14, DNAGold-coated magnetic NPNone, using magnetic fieldThiolated ONT primer50 (GMNP)Fibronectin proteinEhrlich carcinomain vivo[122]
AS1411, DNAChitosan-ss-PEEUATLR4-siRNA, DoxorubicinDirect, covalent124.6 ± 1.068NucleolinA549 cellsin vitro + in vivo[123]
FKN-S2, DNAPEG-aptamer micelleNone or AptamerssDNA-amphiphileNo dataFractalkineColon adeno-carcinomain vitro + in vivo[124]
No name, DNAUrsolic acid, DoxorubicinUrsolic acid, DoxorubicinElectrostatic interactions≈108.9HER2HER2-carrying cells in vitro + in vivo[125]
No name, DNAPEG-SPIONDoxorubicinDirect, covalent5–64Mucin-1MCF-7 cellsin vitro[126]
Two, DNANMOFDoxorubicinHybridization≈130Nucleolin, VEGFMDA-MB-231in vitro[127]
5TR1, DNAPEI-PEG and Na2SeO3Epirubicin and an aptamerCovalent, to PEGNo dataMucin-1 MCF-7 and C26 cellsin vitro + in vivo[128]
No name, DNALiposomeDoxorubicinAmino- carboxyl 170 ± 25HER3MCF-7 breast cancer cellsin vitro + in vivo[129]
No name, DNADNA nano-ringDoxorubicinIncorporated in DNA ring≈29 (DNA ring)Mucin-1MCF-7 breast cancer cellsin vitro[130]
A10–3.2, RNACationic nanobubbleFoxM1 siRNADirect, covalent479.83 ± 24.50PSMALNCaP cellsin vitro + in vivo[131]
No name, DNADNA micelleDoxorubicin, KLA peptideNo data371Mucin-1MCF-7 cellsin vitro + in vivo[132]
No name, DNALipid-polymerSalinomycinThiolated, direct96.3 ± 9.8CD20Melanoma stem cellsin vitro + in vivo[133]
No name, RNAPolymer-lipidSalinomycinThiolated, direct95EGFROsteosarcoma CSCsin vitro[134]
trCLN3, DNALipidated GC-rich DNA hairpinDoxorubicin, 2′,6′-dimethyl azobenzeneLipid-mediated self-assembly21.2 ± 1.5cMetcMet-expressing H1838 cellsin vitro[135]
TLS1c, DNALiposomeCabazitaxelAvidin-biotin interaction90.10 ± 2.71MEAR cellsHepatomain vitro + in vivo[136]
No name, DNAPBABTDocetaxelDirect, covalent274.7 ± 46.1HER2Epithelixal ovarian cancerin vitro + in vivo[137]
No name, DNABSA-PEG-Fe3+Mn, Doxorubicin GAG-linker, base-matchNo dataGlut-1HepG-2 cellsin vitro + in vivo[138]
AS1411TD-PEC- chitosanmiR-145Electrostatic bonds with chitosan40–270NucleolinMCF-7 cellsin vitro + in vivo[139]
No name, DNADNAALK-siRNA, DoxorubicinDirect, covalent59CD30ALCLin vitro + in vivo[140]
No name, DNAHuman IgGMicroRNADirect, covalent595Mucin-1Non-small cell lung cancerin vitro + in vivo[141]
S15, DNAQuantum dotsNoneDirect, covalentNo dataNSCLCA549 cellsin vitro[142]
A15, CL4; RNALipid-polymerSalinomycinDirect, covalent110.2 ± 12.1CD133, EGFROsteosarcoma cells and CSCsin vitro + in vivo[143]
No name, DNAPEG-Au- PAMAMCurcuminCovalent, C6 linker5.23 ± 4.12Mucin-1HT29 and C26 cellsin vitro + in vivo[144]
No name, RNALiposomeDocetaxelCovalent, to DSPE-PEG116.5 ± 9.3CD133A549 cellsin vitro + in vivo[145]
5TR1, DNAPEGylated liposomeDoxorubicinNo data120 ± 1.8Mucin1C26 cellsin vitro + in vivo[146]
AS1411, DNABovine serum albuminDoxorubicinDirect, amidation163 ± 2.5NucleolinMCF-7 cellsin vitro[147]
No name, DNACopper oxidemRNA 29bDirect, amide linking≈40Mucin 1A549 cellsin vitro[148]
Sgc8c, DNAFe3O4-carbonDoxorubicinDirect, covalentNo dataNo dataA549 cellsin vitro + in vivo[149]
A9, RNAGoldNone (PTT)No data≈70PSMALNCaP cellsin vitro[150]
No name, DNAGold nanoshellNone (PTT)Direct, thiol–Au bondsNo dataMucin 1A549, MCF-7 3D cell culturein vitro[151]
C10.36, DNAPAM (peptide + DNA ONT) PeptideBase pairing110 ± 30HBLLB-cell leukemia cellsin vitro[152]
No name, RNALP-DNASATB1 siRNAThiolated, direct161.2 ± 11.3EGFRChoriocarcinomain vivo[153]
AS1411, DNAPEGylated PLGAanti-miR-21, cisplatin (CIS)Direct, covalent142.4 ± 5.9 106.6 ± 5.9NucleolinCIS-resistant A2780 cellsin vitro[154]
No name, RNALipid-PLGAAll-trans retinoic acidThiolated, direct129.9CD133Lung cancer initiating cellsin vitro[155]
S15, DNAPEG-PCLPaclitaxelDirect, amide linking≈15NSCLCA549 cellsin vitro[156]
S2.2, DNAElastin-like polypeptidePaclitaxelVia gene A’ proteinNo dataMucin-1MCF-7 cellsin vitro[157]
5TR1, DNAPβAE and PLGAEpirubicin, antimir-21Direct, covalent210.4 ±10.14Mucin-1MCF-7 cellsin vitro + in vivo[158]
No name, RNALipid-polymerAll-trans retinoic acidThiolated, direct129.9CD133Osteosarcoma initiating cellsin vitro[159]
No name, DNACalcium carbonateEpirubicin, and melittinAvidin-biotin interaction>300Mucin-1MCF-7 and C26 cellsin vitro + in vivo[160]
ACE4Diacetylene-PEGNone 31 G spacer, base pairing≈13Annexin A2MCF-7 cellsin vitro[161]
No name, DNAHuman IgGGenistein and miRNA-29bC12 spacer, covalent598 ± 34.1Mucin-1A549 cell linein vitro[162]
No name, DNALipid-quantum dotsiRNADirect, covalentNo dataEGFRTriple-negative breast cancerin vitro + in vivo[163]
HB5, DNAHuman serum albuminCurcumin Direct, covalent281.1 ± 11.1HER2SK-BR-3 cellsin vitro[164]
AS1411, DNAMagnetic SPION/MSNDoxorubicinDirect, covalent89NucleolinMCF-7 cellsin vitro[165]
AS1411, DNAAlbumin-IONP/GNPDoxorubicinDirect, covalent≈120NucleolinMCF-7 and SKBR3 cellsin vitro[166]
C2NP, DNAPEG-PLGADoxorubicinDirect, covalent168.07 ± 2.72CD30Large cell lymphomain vitro[167]
AS1411, DNALiposomePaclitaxel and PLK1 siRNADSPE-PEG-MAL121.27 ± 2.51NucleolinMCF-7 cellsin vitro + in vivo[168]
AS1411, DNALiposomeAptamer- doxorubicinNot Applicable≈128.6Nuclear nucleolinMCF-7/Adr cellsin vitro[169]
AS1411, DNAPEGylated liposome5-fluorouracilVia PEG linker190 ± 15Nuclear nucleolinBasal cell carcinomain vitro[170]
HApt, DNAβ-CD-capped MSNDoxorubicinThiolated to β-CD218.2 ±6.1HER2HER2-positive cellsin vitro[16]
AS1411, DNASPIONDaunomycin, TMPyPAmide bond, direct15–20NucleolinA549 and C26 cellsin vitro[171]
S1.5, DNAPEGylated PLGADocetaxelCarbodiimide coupling142.7± 12.3HPATNBC cellsin vitro + in vivo[172]
No name, DNAMesoporous MnO2HMMEDirect, covalent≈200Mucin 1MCF-7 cellsin vitro + in vivo[173]
AS1411, DNAPLGA, PVPDoxorubicinDirect, covalent≈87.168NucleolinA549 cellsin vitro + in vivo[174]
No name, DNADNA hydrogelCpG ONT and DoxorubicinCovalent, to CpG ONT50.1 ± 2.82Mucin-1MCF-7 cellsin vitro[175]
AS1411, DNA; (HA)Micro-emulsionShikonin and docetaxelDirect, thiolated ≈30Nucleolin; (CD44)Gliomain vitro, model[176]
No name, DNACationic liposomemiR-139–5pDirect, covalent150.3 ±8.8EpCAMColorectal Cancerin vitro + in vivo[177]
Sgc8, DNAMSNDoxorubicinDirect, covalent103.24 PTK7CCRF-CEM cellsin vitro[178]
GMT8, Gint4.T; DNADNAPaclitaxelDirect, covalent17.78U87MG cell, PDGFRβGlioblastomain vitro[179]
AS1411, DNADerived from erythrocytesDoxorubicin, siRNACovalent to cholesterol via 6-A bases≈100NucleolinMDR MCF-7 cellsin vitro[180]
TA6, DNADNA nanotrainAKT inhibitor, DoxorubicinDirect, covalentNo dataCD44 Breast cancer stem cellsin vitro + in vivo[181]
A15, RNALiposomeCurcuminDirect, thiol-maleimide86.6 ± 4.5CD133DU145 cellsin vitro + in vivo[182]
AS1411, DNASilver-PEGNone (irradiation)Amide bond to PEG18.82 ± 2.1NucleolinGliomain vitro + in vivo[183]
U2, DNAGoldNoneDirect, Au-S bond≈60.23EGFRGlioblastomain vitro + in vivo[184]
M49, DNAPEGylated liposomeDoxorubicinCovalent, to PEGNo dataCD200R14THM breast carcinomain vivo[185]
TC01, Sgc4f, and Sgc8; DNADNA ONTDoxorubicinDNA ONT hybridizationNo dataMultiple cancers and PTK7CCRF-CEM cellsin vitro + in vivo[186]
No name, DNADNA origamiAntisense ONT, doxorubicinExtended sequences4.17 ± 0.12 (height)Mucin-1HeLa/ADR cellsin vitro[187]
LZH5B, DNADNA nanotrainDoxorubicinHybridizationNo dataHepG2 cellHepG2 cell linein vitro[188]
No name, DNASPION@SiO2DoxorubicinDirect, covalent5–27 Mucin-1MCF-7 cellsin vitro[189]
AS1411, DNAUpconversion nanoparticleProtoporphyrin IXDirect, covalent120 ± 4NucleolinHeLa and A549 cellsin vitro[190]
AS-14, AS-42; DNASPMFNDoxorubicinGlycosidic linkagesNo dataFN, HSP71Ehrlich carcinoma cellsin vitro + in vivo[191]
AS1411, DNAGoldAnti-miR-155PolyA linker sequence≈30NucleolinMCF-7 cellsin vitro[192]
L5, etc., DNAPLGADocetaxelDirect, covalent156.9 ± 42.97Not clear yetHepG2 and Huh-7 cellsin vitro + in vivo[193]
L5, DNAPLGADocetaxelDirect, covalent211.9–236.1TAG-72HepG2 and Huh-7 cellsin vitro[194]
LXL, DNARNA hydrogelsiRNA and miRNANo data≈200MDA-MB-231 cellTriple-negative breast cancerin vitro + in vivo[195]
AS1411, DNACaCO3 and protamineCRISPR-Cas9 plasmidCovalent, to HA230–320NucleolinH1299 cellsin vitro[196]
No name, RNA Hollow gold nanosphereDoxorubicinThiolated≈42 (25–55)CD30Karpas 299 cellsin vitro[197]
C2NP, DNADNA nanotubeDoxorubicinBy extending staples140 × 14 (L × W)CD30K299 cellsin vitro[198]
No name, DNAssDNA-ELPDocetaxelCovalent, to ELP10–40Mucin-1MCF-7 cellsin vitro[199]
No name, DNAMagnetic nanosphereDoxorubicinStreptavidin-biotinNo dataEpCAMMCF-7 cells (CTCs)in vitro[200]
AS1411, DNADNA nanotrainsDOX, EPI, and DAUBase pairingNo dataNucleolinHeLa cellsin vitro[201]
No name, RNAProtamineDoxorubicin, ALK-siRNANon-covalentNo dataCD30ALCLin vitro[202]
AS1411, DNATiO2 nanofiber with BSANoneStreptavidin-biotin81.33 ± 25.70AS1411, DNAMCF-7 cells (CTCs)in vitro[203]
AS1411, DNAGold and liposomeMorinCovalent, Au-S No dataNucleolinSGC-7901 cellsin vitro + in vivo[204]
AS1411, DNAGO NanosheetBerberine derivativeNH2-(CH2)6 linker30–50 × 2–3NucleolinA549 cellsin vitro[205]
AS1411, DNADNA Holliday junctionDoxorubicinPhospho-diester bond12.45 ± 2.16NucleolinCT26 colon cancer cellsin vitro[206]
Syl3c, DNAPEGylated liposomeDoxorubicinCovalent, to PEG110 ± 5EpCamC26 Colon Carcinomain vitro + in vivo[207]
No name, DNAAg-MOF-RBCmPFK15Inserted into RBCm≈109CD20B-cell lymphomain vitro + in vivo[208]
No name, DNAPCL-MMA/MPEG-MASIDoxorubicinCovalent, to NHS group≈124EpCAMHT29 cellsin vitro[209]
AS1411, DNAFO-loaded MOF-RBCmUsing PDT and CDT effectsInserted via cholesterol110–140NucleolinKB cellsin vitro + in vivo[210]
MAGE-A3, DNANIR PLNAfatinibBy a disulfide bond225MAGENSCLCin vitro + in vivo[211]
A10-3.2, RNALipid-polymer hybridCurcumin and CabazitaxelCovalent, to PEG121.3 ± 4.2PSMAProstate cancerin vitro + in vivo[212]
A6, DNADOTAP, Mal-PEG, cholesterol, PLGA P-gp siRNACovalent, to Mal-PEGNo dataHER2DOX-resistant 4T1 cellsin vitro[213]
Wy5a, DNAPLGA-PEG-COOHDocetaxel Amide bond with spacer≈154.3PC-3 cellProstate cancerin vitro + in vivo[214]
The aptamers in the table are listed in the order they appear in the literature. ⱡ Size of the nanoparticles after aptamer conjugation. For spherical nanoparticle, the number is the diameter of the particle; for nanotubes or nanosheets, the measurement uses a × symbol. # Direct conjugation means there is no bridge, spacer, or linker molecule/sequence between the aptamer and the nanoparticle. * The aptamer-conjugated gold nanorods were surface modified with BSA through electrostatic interactions.
Table
Table 2. Aptamer-functionalized nanoparticles classified by nanomaterials and payloads.
Table 2. Aptamer-functionalized nanoparticles classified by nanomaterials and payloads.
Type of NanoparticlePayloadsAptamersTargetsCancersReferences
Polymer based nanoparticlesPLA-PEGRhodamine-labeled dextranA10PSMA Prostate cancer, [18]
PLGA-PEGCisplatin, Docetaxel, Doxorubicin, Gemcitabine, Paclitaxel, Salinomycin, Vinorelbine, PI3K-mTOR inhibitor, anti-miR-21, and cisplatin,A10, A15, AS1411, C2NP, EpCAM-Ap, Gint4.T, PSMA-Ap, S1.5, Wy5aCD30, CD133, EpCAM, HPA, Nucleolin, PC-3 cell, PGFRβ, PSMABreast cancer, glioblastoma, glioma, large cell lymphoma, lung cancer, NSCLC, osteosarcoma, cisplatin-resistant ovarian cancer, prostate cancer, TNBC[22,29,35,57,71,76,81,102,6,122,163,176,181,223]
PLGADocetaxel, Paclitaxel, Nutlin-3a, Salinomycin, Triplex forming oligonucleotide, PropranololA10, A15, AS1411, L5, S2.2, EpCAM-ApPSMA, CD133, EGFR, MUC1, Nucleolin, TAG-72Breast cancer, hepatocellular carcinoma, hemangioma, human glial cancer, prostate cancer[34,42,83,105,128,203]
PEG-PCLDocetaxelAS1411, GMT8, S15Nucleolin, NSCLC, U87 cellsGlioblastoma, glioma, lung cancer[43,45,165]
H40-PLA-PEGDoxorubicinA10PSMAProstate cancer[42]
pPEGMA-PCL-pPEGMADoxorubicinAS1411NucleolinPancreatic carcinoma[52]
PEG-PAMAMMicroRNAA10–3.2PSMAProstate cancer[58]
PF127-β-CD-PEG-PLADoxorubicinAS1411NucleolinBreast cancer[60]
PEIEpCAM-siRNAEpCAM-ApEpCAMBreast cancer, retinoblastoma[63]
GPNGefitinibEts1-ApEts1NSCLC[69]
PLL-alkyl-PEIshRNAAS1411NucleolinLung cancer[80]
HPAEGDoxorubicinAS1411NucleolinBreast cancer[94]
M-PLGA–TPGSDocetaxelAS1411NucleolinCervical cancer[98]
PBABTDocetaxelHER2-ApHER2Ovarian cancer[137]
PβAE and PLGAEpirubicin and antimir-215TR1MUC1Breast cancer[158]
PLGA, PVPDoxorubicinAS1411NucleolinLung cancer[174]
PCL-MMA/MPEG-MASIDoxorubicinEpCAM-ApEpCAMColorectal cancer[209]
Lipid based nanoparticlesLiposomeCurcumin, Doxorubicin, Cabazitaxel, Cisplatin, CRISPR-Cas9 plasmid, Docetaxel, Doxorubicin, Paclitaxel, and PLK1 siRNA, TSPA10, A15, AS1411, HER3-Ap, PSMA-Ap, TLS1cCD133, HER3, MEAR cells, Nucleolin, PSMA, PDGFRBreast cancer, DOX-resistant breast cancer, Hepatoma, lung cancer, prostate cancer, [33,50,58,65,113,138,145,154,178,191]
PEGylated-liposome5-FU, Doxorubicin, Anti-BRAF siRNA5TR1, AS1411, M49, Syl3c, TSA14,CD200R1, EpCAM, Mucin1, Nucleolin, TUBO cellsBasal cell carcinoma, breast cancer, colon carcinoma, melanoma[50,90,146,170,185,207]
DOTAP:DOPE liposomeDoxorubicinSRZ14T1 cellsBreast cancer[76]
Cationic liposomemiR-139–5pEpCAM-ApEpCAMColorectal Cancer[177]
Chitosan based nanoparticlesChitosanSN38MUC1-ApMUC1Colon cancer[55]
Chitosan and HASN38MUC1-ApMUC1Colorectal adenocarcinoma[78]
HAS-CSPaclitaxelMUC1-ApMUC1Breast cancer[100]
Dendrimer based nanoparticlesDendrimerMicroRNAS6, sgc8cA549 cell, CCRF-CEMALL, NSCLC [23,79]
ONT-PAMAM dendrimerDoxorubicinA9PSMAProstate cancer[29]
PEG-PAMAM dendrimer5-fluorouracil, CamptothecinAS1411NucleolinColorectal cancer, Gastric cancer[101,105]
DGL-PEGDoxorubicin, ATP-aptamerAS1411, Cyt c-ApNucleolin, Cyt cCervical cancer[102]
Alkyl PAMAM dendrimerBcl-xL shRNAAS1411NucleolinLung cancer[112]
Hydrogel based nanoparticlesMCS nanogelDoxorubicinLNCaP-ApLNCaP cellProstate cancer[109]
DNA HydrogelCpG ONT and DoxorubicinMUC1-ApMUC1Breast cancer[175]
RNA HydrogelsiRNA and miRNALXLMDA-MB-231 cellTriple-negative breast cancer[195]
Nucleic acid based nanoparticlesDNA icosahedraDoxorubicinMUC1-ApMUC1Breast cancer[27]
Aptamer DNAAntisense ONT against P-gpsgc8cCCRF-CEM cellALL[45]
GC-rich dsDNADoxorubicinAS1411NucleolinDrug-resistant breast cancer[92]
DNA dendrimerEpirubicinMUC1-Ap, AS1411-ApMUC1, AS1411Breast and colon cancers [95]
3WJ-RNADoxorubicinEndo28Annexin A2Ovarian cancer[99]
DNA nano-ringDoxorubicinMUC1-ApMUC1Breast cancer[130]
Lipidated GC-rich DNA hairpinDoxorubicin and 2′,6′-dimethyl-azobenzenetrCLN3cMetcMet-expressing lung cancer[135]
DNAALK-siRNA, Doxorubicin, PaclitaxelCD30-Ap, Gint4.T, GMT8, Sgc4f, Sgc8, TC01cancer cells, CD30, PDGFRβ, PTK7, U87MG cellALCL, ALL, Glioblastoma[140,179,186]
DNA origamiAntisense ONT, doxorubicinMUC1-ApMUC1MDR cervical cancer[187]
DNA nanotubeDoxorubicinC2NPCD30Human anaplastic large cell lymphoma[198]
DNA nanotrainAKT inhibitor, DAU, DOX, DNR, EPI, GoldAS1411, LZH5B, Sgc8, TA6CD44, HepG2 cell, nucleolin, PTK7ALL, Breast cancer stem cell, cervical cancer, liver cancer[46,181,188,201]
DNA Holliday junctionDoxorubicinAS1411NucleolinColon cancer[206]
Protein/peptide based nanoparticlesAlbuminCisplatin, Curcumin, DoxorubicinAS1411, EGFR-Ap, HB5EGFR, HER2, nucleolinBreast cancer, cervical cancer[85,147,164]
Human IgGGenistein, miRNA-29bMUC1-ApMUC1NSCLC[86,141,162]
Elastin-like polypeptidePaclitaxelS2.2MUC1Breast cancer[157]
Human serum albumin
ProtamineDoxorubicin, ALK-siRNACD30-ApCD30Lymphoma[202]
Polymer and lipid hybridsPLGA-lecithin-PEGPaclitaxel, CurcuminAS1411, EpCAMNucleolinBreast cancer, colorectal adenocarcinoma[32,51]
PLGA-lipid-PEGDocetaxelXEO2miniPC3 cellsProstate cancer[31]
Lipid-polymer liposomesiRNAA6HER2Breast cancer[106]
Polymer-lipidAll-trans retinoic acid, Curcumin and Cabazitaxel, SalinomycinA10–3.2, A15, CD20-Ap, CD133-Ap, CL4, EGFR-ApCD20, CD133, EGFR, PSMAMelanoma, osteosarcoma, prostate cancer[133,134,143,159,212]
Lipid-PLGAAll-trans retinoic acidCD133-ApCD133Lung cancer[155]
DOTAP, PLGA, cholesterol, Mal-PEG P-gp siRNAA6HER2DOX-resistant breast cancer[213]
Polymer and chitosan hybridsPLGA-chitosanEpirubicin5TR1MUC1Breast cancer, colon carcinoma[111]
Chitosan-ss-PEEUATLR4-siRNA, DoxorubicinAS1411NucleolinLung cancer[123]
Chitosan and lipid hybridsChitosan-liposomeErlotinibEGFR-ApEGFREGFR-mutated cancer cells[107]
Chitosan-liposomePFOB and ErlotinibEGFR-ApEGFRNSCLC[116]
Nucleic acid and peptide hybridsKLA-DNA micelleDoxorubicin+KLAMUC1-ApMUC1Breast cancer[132]
PAM (peptide +DNA ON)PeptideC10.36HBLLB-cell leukemia[152]
ssDNA-ELPDocetaxelMUC1-ApMUC1Breast cancer[199]
Other organic nanoparticlesAtelocollagenMicroRNAA10–3.2PSMAProstate cancer[59]
Tocopheryl PEG-PβAEDocetaxelAS1411NucleolinOvarian cancer[77]
PEG-aptamer micelleNone or AptamerFKN-S2FractalkineColon adeno-carcinoma[124]
Ursolic acidDoxorubicinHER2-ApHER2HER2-carrying cells[125]
TD-PEC-chitosanmiR-145AS1411NucleolinBreast cancer[139]
LP-DNASATB1 siRNAEGFR-ApEGFRChoriocarcinoma[153]
Diacetylene-PEGNoneACE4Annexin A2Breast cancer[161]
Inorganic nanoparticlesAu-AgPhotothermal therapysgc8cCCRF-CEM cellALL[21]
GoldAnti-miR-155, Antisense ONT, Daunorubicin, Doxorubicin, TMPyP4, PTTA9, AIR-3A, AS1411, As42, CD30-Ap, CD33/CD34-Ap, KW16–13, MUC1-Ap, sgc8c, U2CCRF-CEM, CD30, CD33/CD34, EGFR, Ehrlich’s ACC, IL-6R, MCF10CA1h, MUC1, nucleolin, PSMAALL, AML, breast cancer, cervical cancer, Ehrlich carcinoma, glioblastoma, human breast duct carcinoma, lymphoma, lung cancer, prostate cancer[15,44,53,54,66,82,87,88,108,120,150,151,184,192,197]
Mesoporous silicaDoxorubicin, Epirubicin, Fluorescein, gold nanorodsAS1411, Sgc8, EpCAM-Ap, MUC1-ApNucleolin, PTK7, EpCAM, MUC1ALL, breast cancer, human T cell leukemia, colon cancer[35,38,39,40,89,114,178]
Mesoporous silica–carbonDoxorubicinHB5 HER2Breast cancer[64]
Graphene oxide-goldDoxorubicin, None (PTT)S2.2, MUC1-ApMUC1Breast cancer, lung cancer[65,73]
Graphene oxide-MSNDoxorubicinCy5.5-AS1411NucleolinBreast cancer[71]
ZnODoxorubicinS2.2MUC1Breast cancer[75]
GQD-FMSNDoxorubicinAS1411NucleolinCervical cancer[81]
IronNone (HTT)MA3MUC1Breast cancer[84]
Au-Fe3O4NoneVEGF-ApVEGFOvarian cancer[117]
Copper oxidemRNA 29bMUC1-ApMUC1Lung cancer[148]
Calcium carbonateEpirubicin, and melittinMUC1-ApMUC1Breast cancer[160]
Mesoporous MnO2HMMEMUC1-ApMUC1Breast cancer[173]
Silver-PEGIrradiationAS1411NucleolinGlioma[183]
Graphene oxide sheetsBerberine derivativeAS1411NucleolinLung cancer[205]
Quantum dot based nanoparticlesQuantum dotsNoneS15NSCLCLung cancer[142]
QD-PMAT-PEIsiRNAPSMA-ApPSMAProstate cancer[30]
Lipid-quantum dotsiRNAEGFR-ApEGFRTriple-negative breast cancer[163]
Magnetic nanoparticlesSPIONEpirubicin, Doxorubicin, Daunomycin and TMPyP5TR1, A9, A10, AS1411, DNA-RNA hybridMUC1, Nucleolin, PSMAColon cancer, breast cancer, lung cancer, prostate cancer[22,28,43,91,171]
Dextran-ferric oxideNoneHER2-ApHER2Human adenocarcinoma[47]
Au-SPIONNoneMUC1-ApMUC1Colon cancer[83]
Iron oxideNone (HTT)FGFR1-ApFGFR1Human osteosarcoma[103]
Gold-coated magnetic NPNoneAS-14Fibronectin proteinEhrlich carcinoma[122]
PEG-SPIONDoxorubicinMUC1-ApMUC1Breast cancer[126]
Fe3O4-carbonDoxorubicinSgc8c-ApSgc8cLung cancer[149]
Magnetic SPION/MSNDoxorubicinAS1411NucleolinBreast cancer[165]
SPMFNDoxorubicinAS-14 and AS-42FN and HSP71Ehrlich carcinoma[191]
SPION@SiO2DoxorubicinMUC1-ApMUC1Breast cancer[189]
Magnetic nanosphereDoxorubicinEpCAM-ApEpCAMBreast cancer[200]
Other inorganic nanoparticlesGd:SrHapDoxorubicinAS1411NucleolinBreast cancer[37]
Organic and inorganic hybridsMOF-UCNP DoxorubicinAS1411NucleolinBreast cancer[68]
Gold-liposomeDocetaxel, MorinAS1411, S2.2Nucleolin, MUC1Breast cancer, gastric cancer[119,213]
Aminopropyl MSNSafranin OMUC1-ApMUC1Breast cancer[115]
MPC-PAA/PEIDoxorubicinMUC1-ApMUC1Breast cancer, lung cancer[118]
PDA/PEG- coated MSNDM1EpCAM-ApEpCAMColorectal cancer[121]
NMOFDoxorubicinAS1411, VEGF-ApNucleolin, VEGFBreast cancer[127]
PEI-PEG and Na2SeO3Epirubicin and an aptamer5TR1MUC1Breast cancer[128]
BSA-PEG-Fe3+Mn, DoxorubicinGlut-1-ApGlut-1Liver cancer[138]
PEG-Au- PAMAMCurcuminMUC1-ApMUC1Colon adenocarcinoma[144]
Albumin-IONP/GNPDoxorubicinAS1411NucleolinBreast cancer[166]
β-CD-capped MSNDoxorubicinHAptHER2HER2-positive cells[16]
CaCO3 and protamineCRISPR-Cas9 plasmidAS1411NucleolinNSCLC[196]
TiO2 nanofiber with BSANoneAS1411NucleolinBreast cancer CTCs[203]
OthersCationic nanobubbleFoxM1 siRNAA10–3.2PSMAProstate cancer[131]
Micro-emulsionShikonin and docetaxelAS1411 and HANucleolin and CD44Glioma[176]
RBC membraneDoxorubicin, siRNAAS1411NucleolinMDR breast cancer[180]
Upconversion nanoparticleProtoporphyrin IXAS1411NucleolinCervical cancer, lung cancer[190]
Ag-MOF-RBCmDoxorubicinCD20-ApCD20B-cell lymphoma[208]
FO-loaded MOF-RBCmUsing PDT and CDT effectsAS1411NucleolinKB Cell Line[210]
NIR PLNAfatinibMAGE-A3MAGENSCLC[211]
For aptamers that do not have a name, “target-Ap” is used to represent the aptamer; for example, EpCAM-Ap represents the aptamer that targets EpCAM.
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Fu, Z.; Xiang, J. Aptamer-Functionalized Nanoparticles in Targeted Delivery and Cancer Therapy. Int. J. Mol. Sci. 2020, 21, 9123. https://doi.org/10.3390/ijms21239123

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Fu Z, Xiang J. Aptamer-Functionalized Nanoparticles in Targeted Delivery and Cancer Therapy. International Journal of Molecular Sciences. 2020; 21(23):9123. https://doi.org/10.3390/ijms21239123

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Fu, Zhaoying, and Jim Xiang. 2020. "Aptamer-Functionalized Nanoparticles in Targeted Delivery and Cancer Therapy" International Journal of Molecular Sciences 21, no. 23: 9123. https://doi.org/10.3390/ijms21239123

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