Aptamer Hybrid Nanocomplexes as Targeting Components for Antibiotic/Gene Delivery Systems and Diagnostics: A Review

Figures & data

Table 1 Different Properties Between Antibodies and Aptamers

Aptamer	Antibody
Unlimited shelf life (several months)	Limited shelf life (few months)
High tissue penetration (small size, 3 nm)	Low tissue penetration (large size, 10–15 nm)
High specificity and affinity	High specificity and affinity
High stability in pH and temperature	Low stability in pH and temperature
Low immunogenicity	High immunogenicity
Variety of modification by diverse molecules	Hard to be modified
Cost of production of aptamer is less expensive	Cost of production of antibody is expensive
Presence of nuclease susceptibility (need for modification)	Absence of nuclease susceptibility

Figure 1 Schematic illustration of the recognition process of S. aureus using a AuNCs@Van and Apt-MB (I) dual recognition assay, and the characterization (II) (A–F) represents the optical, fluorescence and transmission electron microscopy characterization of this synthesized particle. The figure was reprinted with permission from Cheng D, Yu M, Fu F, et al. Dual recognition strategy for specific and sensitive detection of bacteria using aptamer-coated magnetic beads and antibiotic-capped gold nanoclusters. Analytical Chemistry. 2016;88(1):820–825. Copyright © 2016 American Chemical Society.⁴³

Table 2 Types of Aptamer-Based Nanostructures in Diagnostics with Their Advantages and Limitations

Aptamer-Based Nanostructures	Size of Nanostructures	Detection Methods	LOD	Advantages	Limitations	Ref
Au NPs/Graphene (Au NPs/Gr)	500 nm	Colorimetric detection	0.01–0.5 μM and 0.01–1.0 μg/L	Detection of various targets by this aptamer, rapid colorimetric assay, design of specific aptamer	Investigation of other lengths of aptamers	^Citation60
Anti-IL-6 Aptamer-AuNPs	15 and 50nm	Colorimetric detection	1.95 μg/·mL	Successful detection of murine IL-6 (in the μg·mL^−1 range) in buffers and a biological sample matrix	Low sensitiv-ity, more work is needed to increase the sensitivity to detect IL-6 in healthy serum/plasma	^Citation61
Graphene quantum dots (GQDs) -gold nanorods (AuNRs)	2–3 nm size of GQDs, 2nm size of AuNRs	Electrochemical impedance spectroscopy (EIS), cyclic voltammetry, differential pulse voltammetry	0.14 ng/mL	Detect PSA in human blood serum with high sensitivity and repeatability, stability, cost effectiveness	Using the three analytical methods from this study to measure the signal at the same time, but can also be used for better measurement	^Citation62
Apt-Fe3O4@mTiO2	200 nm	-	10 to 2000 CFU/mL	Rapid and sensitive detection of pathogenic bacteria, high selectivity and strong affinity of aptamers	Although both systems exhibit effective monitoring and high sensitivity, the expensive cost of detection limits their widespread use	^Citation63
MNPs-specific aptamer	20nm size of Fe3O4 MNPs	Colorimetric detection	7.5×10^5 CFU/mL	Use of specific aptamers, easy separation, low cost	Low LOD, need to enhance the LOD and to increase the cross-reactiv- ity to other pathogens	^Citation64

Figure 2 AuNPs-aptamer was capped on the MSA surface due to the binding reaction of ATP aptamer to the adenosine molecule. The delivery of the entrapped guest (fluorescein) was selectively triggered by an effective displacement reaction in the presence of the target molecule (ATP). Reprinted with permission from Zhu CL, Lu CH, Song XY, Yang HH, Wang XR. Bioresponsive controlled release using mesoporous silica nanoparticles capped with aptamer-based molecular gate. J Am Chem Soc. 2011;133(5):1278-1281. Copyright (2020) American Chemical Society.⁷³

Figure 3 Schematic representation of cationic nanoparticles for targeted delivery of siRNA-aptamer chimeras. Immobilization of preformed siRNA-aptamer chimeras onto positively charged QD-PMAT-PEI nanoparticles. The aptamer block collapsed on the carrier results in reduced binding activity. Two-step immobilization of chimeras on a cationic nanoparticle surface. siRNA molecules with a thiol-reactive terminal group are first adsorbed on the QD-PMAT-PEI surface to reduce the positive charge; subsequently aptamers with a single thiol group are brought in to form siRNA-aptamer chimeras on the nanoparticle surface. Adapted with permission from Bagalkot V, Gao X. siRNA-aptamer chimeras on nanoparticles: preserving targeting functionality for effective gene silencing. ACS Nano. 2011;5(10):8131-8139.^82,138 Copyright (2011) American Chemical Society.

Figure 4 Schematic of the newly synthesized aptamer-PEI-siRNA nanocomplex (PEI-EpApt-SiEP) and its function to silence the target gene and decrease cell proliferation. The figure was reproduced from Subramanian N, Kanwar JR, Athalya P, et al. EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex. J Biomed Sci. 2015;22(1):4. Copyright © Subramanian et al; licensee BioMed Central. 2015. Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0).⁹⁸

Figure 5 SEM images of carbon nanotube: DNA complexes formed at a 6:1 charge ratio: (A-C) MWNT-NH3 +:DNA; (D-F) SWNT-NH3 +:DNA. Reprinted with permission from Singh R, Pantarotto D, McCarthy D, et al. Binding and condensation of plasmid DNA onto functionalized carbon nanotubes: toward the construction of nanotube-based gene delivery vectors. J Am Chem Soc. 2005;127(12):4388-4396.^114,139 Copyright (2020) American Chemical Society.

Table 3 Types of Aptamer-Based Structures in Gene Delivery Systems

Aptamer-Based Structure	Targeted Cells	Agents	Results	Ref
RNA aptamer EpDT3	HepG2 cells	Tumor-suppressor gene of PTEN	Increase the antitumor effect on liver cancer, decrease disadvantages of naked Ad5-PTEN, selective and accurate target ability to EpCAM-positive HepG2 cells in vivo	^Citation135
PEI- sgc-8c aptamer	MOLT-4 cells and U266 cell lines	PDNA	A six- to eight-fold increase in transfection efficiency by pDNA/PEI/sgc-8c aptamer polyplexes than the pDNA/PEI polyplex, a higher transfection efficiency without significantly induced cytotoxicity due non-covalently conjugation to PEI by electrostatic interactions	^Citation136
PEI/ARAD	HeLa cells	PDNA (p53)	Lower cell toxicity, high gene transfection efficiency	^Citation137
PEI-PEG-Wy5a Aptamer	PC-3 prostate cancer cells, DU145 cells	PDNA	PEI-PEG-Wy5a appropriate for prostate cancer-specific gene delivery, Wy5a increase uptake of the complex into the tumors than an AS1411 aptamer, formation of stable complexes with pDNA	^Citation138
5TR1- aptamer SWCNT-PEG-PEI	MCF-7 and MDA-MB231 cell lines	Bcl-xL shRNA	8.5–10 fold improvement in transfection activity at C/P ratios of 6 than PEI 25 kDa, low cytotoxicity and high gene delivery efficiency	^Citation113
AS1411 aptamer- SWNT-PEG-PEI	AGS and L929 cells	pBcl-xL shRNA-DOX	This targeted delivery system inhibited the progress of nucleolin-abundant gastric cancer cells with high selectivity	^Citation122
Scorpion stingers	SK-BR-3 cells, MDA-MB-231 cells	DNA nano-scorpion nanostructure (termed AptDzy-DNS)	AptDzy-DNS shows high efficiency for targeted gene therapy with good biocompatibility and no side effects	^Citation139

Cheng D, Yu M, Fu F, et al. Dual recognition strategy for specific and sensitive detection of bacteria using aptamer-coated magnetic beads and antibiotic-capped gold nanoclusters. Anal Chem. 2015;88(1):820–825. doi:10.1021/acs.analchem.5b0332026641108

 PubMed Web of Science ®Google Scholar

Tian J. Aptamer-based colorimetric detection of various targets based on catalytic Au NPs/Graphene nanohybrids. Sens Bio-Sensing Res. 2019;22:100258. doi:10.1016/j.sbsr.2019.100258

 Google Scholar

Giorgi-Coll S, Marín MJ, Sule O, Hutchinson PJ, Carpenter KLH. Aptamer-modified gold nanoparticles for rapid aggregation-based detection of inflammation: an optical assay for interleukin-6. Microchimica Acta. 2019;187(1):13. doi:10.1007/s00604-019-3975-731802241

 PubMed Web of Science ®Google Scholar

Srivastava M, Nirala NR, Srivastava SK, Prakash R. A comparative study of aptasensor vs immunosensor for label-free PSA cancer detection on GQDs-AuNRs modified screen-printed electrodes. Sci Rep. 2018;8(1):1923. doi:10.1038/s41598-018-19733-z29386538

 PubMedGoogle Scholar

Shen H, Wang J, Liu H, et al. Rapid and selective detection of pathogenic bacteria in bloodstream infections with aptamer-based recognition. ACS Appl Mater Interfaces. 2016;8(30):19371–19378. doi:10.1021/acsami.6b0667127411775

 PubMed Web of Science ®Google Scholar

Park JY, Jeong HY, Kim MI. Colorimetric detection system for salmonella typhimurium based on peroxidase-like activity of magnetic nanoparticles with DNA aptamers. J Nanomater. 2015;2015.

 Web of Science ®Google Scholar

Zhu C-L., Lu C-H., Song X-Y., Yang H-H., Wang X-R.. Bioresponsive controlled release using mesoporous silica nanoparticles capped with aptamer-based molecular gate. J Am Chem Soc. 2011;133(5):1278–1281. doi:10.1021/ja110094g21214180

 PubMed Web of Science ®Google Scholar

Bagalkot V, Gao X. siRNA-Aptamer Chimeras on Nanoparticles: Preserving Targeting Functionality for Effective Gene Silencing. ACS Nano. 2011;5(10):8131–8139. doi:10.1021/nn202772p21936502

 PubMed Web of Science ®Google Scholar

Lee J, Oh J, Lee E-S, Kim Y-P, Lee M. Conjugation of prostate cancer-specific aptamers to polyethylene glycol-grafted polyethylenimine for enhanced gene delivery to prostate cancer cells. J Ind Eng Chem. 2019;73:182–191. doi:10.1016/j.jiec.2019.01.023

 Web of Science ®Google Scholar

Subramanian N, Kanwar JR, Athalya P, et al. EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex. J Biomed Sci. 2015;22(1):4. doi:10.1186/s12929-014-0108-925576037

 PubMedGoogle Scholar

Singh R, Pantarotto D, McCarthy D, et al. Binding and condensation of plasmid DNA onto functionalized carbon nanotubes: toward the construction of nanotube-based gene delivery vectors. J Am Chem Soc. 2005;127(12):4388–4396.15783221

 PubMed Web of Science ®Google Scholar

Wu D, Zhang Y, Xu X, et al. RGD/TAT-functionalized chitosan-graft-PEI-PEG gene nanovector for sustained delivery of NT-3 for potential application in neural regeneration. Acta Biomater. 2018;72:266–277. doi:10.1016/j.actbio.2018.03.03029578088

 PubMed Web of Science ®Google Scholar

Liu Z, Sun X, Xiao S, et al. Characterization of aptamer-mediated gene delivery system for liver cancer therapy. Oncotarget. 2017;9:6.

 Google Scholar

Shahidi-Hamedani N, Shier WT, Moghadam Ariaee F, Abnous K, Ramezani M. Targeted gene delivery with noncovalent electrostatic conjugates of sgc-8c aptamer and polyethylenimine. J Gene Med. 2013;15(6–7):261–269.23794147

 PubMed Web of Science ®Google Scholar

Wang G-H, Huang G-L, Zhao Y, et al. ATP triggered drug release and DNA co-delivery systems based on ATP responsive aptamers and polyethylenimine complexes. J Mater Chem B. 2016;4(21):3832–3841. doi:10.1039/C5TB02764K32263321

 PubMed Web of Science ®Google Scholar

Taghavi S, HashemNia A, Mosaffa F, Askarian S, Abnous K, Ramezani M. Preparation and evaluation of polyethylenimine-functionalized carbon nanotubes tagged with 5TR1 aptamer for targeted delivery of Bcl-xL shRNA into breast cancer cells. Colloids Surf B. 2016;140:28–39. doi:10.1016/j.colsurfb.2015.12.021

 PubMed Web of Science ®Google Scholar

Taghavi S, Nia AH, Abnous K, Ramezani M. Polyethylenimine-functionalized carbon nanotubes tagged with AS1411 aptamer for combination gene and drug delivery into human gastric cancer cells. Int J Pharm. 2017;516(1–2):301–312. doi:10.1016/j.ijpharm.2016.11.02727840158

 PubMedGoogle Scholar