Aptamer-Based Targeted Drug Delivery Systems: Current Potential and Challenges

Fen       He; Nachuan       Wen; Daipeng       Xiao; Jianhua       Yan; Hongjie       Xiong; Shundong       Cai; Zhenbao       Liu; Yanfei       Liu
doi:10.2174/0929867325666181008142831
Abstract

Aptamers are single-stranded DNA or RNA with 20-100 nucleotides in length that can specifically bind to target molecules via formed three-dimensional structures. These innovative targeting molecules have attracted an increasing interest in the biomedical field. Compared to traditional protein antibodies, aptamers have several advantages, such as small size, high binding affinity, specificity, good biocompatibility, high stability and low immunogenicity, which all contribute to their wide application in the biomedical field. Aptamers can bind to the receptors on the cell membrane and mediate themselves or conjugated nanoparticles to enter into cells. Therefore, aptamers can be served as ideal targeting ligands for drug delivery. Since their excellent properties, different aptamer-mediated drug delivery systems had been developed for cancer therapy. This review provides a brief overview of recent advances in drug delivery systems based on aptamers. The advantages, challenges and future prospectives are also discussed.
Keywords: Aptamer, cancer target therapy, drug delivery system, nanomaterials, drug carrier, nano-medicine.
« Previous
[1] 
Ellington, A.D.; Szostak, J.W. In vitro selection of RNA molecules that bind specific ligands. Nature,  1990, 346(6287), 818-822.
[http://dx.doi.org/10.1038/346818a0] [PMID: 1697402] 
[2] 
Tuerk, C.; Gold, L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science,  1990, 249(4968), 505-510.
[http://dx.doi.org/10.1126/science.2200121] [PMID: 2200121] 
[3] 
Biondi, E.; Benner, S.A. Artificially expanded genetic information systems for new aptamer technologies. Biomedicines,  2018, 6(2), 53.
[http://dx.doi.org/10.3390/biomedicines6020053] [PMID: 29747381] 
[4] 
 Dunn, M.R.; Jimenez, R.M.; Chaput, J.C. Analysis of aptamer discovery and technology. Nature Reviews Chemistry, 2017, 1, 0076.
[http://dx.doi.org/10.1038/s41570-017-0076] 
[5] 
Girvan, A.C.; Teng, Y.; Casson, L.K.; Thomas, S.D.; Jüliger, S.; Ball, M.W.; Klein, J.B.; Pierce, W.M., Jr; Barve, S.S.; Bates, P.J. AGRO100 inhibits activation of nuclear factor-kappaB (NF-kappaB) by forming a complex with NF-kappaB essential modulator (NEMO) and nucleolin. Mol. Cancer Ther.,  2006, 5(7), 1790-1799.
[http://dx.doi.org/10.1158/1535-7163.MCT-05-0361] [PMID: 16891465] 
[6] 
Bagalkot, V.; Farokhzad, O.C.; Langer, R.; Jon, S. An aptamer-doxorubicin physical conjugate as a novel targeted drug-delivery platform. Angew. Chem. Int. Ed. Engl.,  2006, 45(48), 8149-8152.
[http://dx.doi.org/10.1002/anie.200602251] [PMID: 17099918] 
[7] 
Subramanian, N.; Raghunathan, V.; Kanwar, J.R.; Kanwar, R.K.; Elchuri, S.V.; Khetan, V.; Krishnakumar, S. Target-specific delivery of doxorubicin to retinoblastoma using epithelial cell adhesion molecule aptamer. Mol. Vis.,  2012, 18, 2783-2795.
[PMID: 23213278] 
[8] 
Taghdisi, S.M.; Abnous, K.; Mosaffa, F.; Behravan, J. Targeted delivery of daunorubicin to T-cell acute lymphoblastic leukemia by aptamer. J. Drug Target.,  2010, 18(4), 277-281.
[http://dx.doi.org/10.3109/10611860903434050] [PMID: 19943768] 
[9] 
Hu, Y.; Duan, J.; Zhan, Q.; Wang, F.; Lu, X.; Yang, X.D. Novel MUC1 aptamer selectively delivers cytotoxic agent to cancer cells in vitro. PLoS One,  2012, 7(2)e31970
[http://dx.doi.org/10.1371/journal.pone.0031970] [PMID: 22384115] 
[10] 
Wang, R.E.; Wu, H.; Niu, Y.; Cai, J. Improving the stability of aptamers by chemical modification. Curr. Med. Chem.,  2011, 18(27), 4126-4138.
[http://dx.doi.org/10.2174/092986711797189565] [PMID: 21838692] 
[11] 
Gelinas, A.D.; Davies, D.R.; Janjic, N. Embracing proteins: structural themes in aptamer-protein complexes. Curr. Opin. Struct. Biol.,  2016, 36, 122-132.
[http://dx.doi.org/10.1016/j.sbi.2016.01.009] [PMID: 26919170] 
[12] 
Zhou, J.; Rossi, J. Aptamers as targeted therapeutics: current potential and challenges. Nat. Rev. Drug Discov.,  2017, 16(3), 181-202.
[http://dx.doi.org/10.1038/nrd.2016.199] [PMID: 27807347] 
[13] 
Volk, D.E.; Lokesh, G.L.R. Development of Phosphorothioate DNA and DNA Thioaptamers. Biomedicines,  2017, 5(3)E41
[http://dx.doi.org/10.3390/biomedicines5030041] [PMID: 28703779] 
[14] 
Röthlisberger, P.; Gasse, C.; Hollenstein, M. Nucleic acid aptamers: emerging applications in medical imaging, nanotechnology, neurosciences, and drug delivery. Int. J. Mol. Sci.,  2017, 18(11)E2430
[http://dx.doi.org/10.3390/ijms18112430] [PMID: 29144411] 
[15] 
Xiang, Q.; Tan, G.; Jiang, X.; Wu, K.; Tan, W.; Tan, Y. Suppression of FOXM1 transcriptional activities via a single-stranded DNA aptamer generated by SELEX. Sci. Rep.,  2017, 7, 45377.
[http://dx.doi.org/10.1038/srep45377] [PMID: 28358012] 
[16] 
Laoukili, J.; Stahl, M.; Medema, R.H. FoxM1: at the crossroads of ageing and cancer. Biochim. Biophys. Acta,  2007, 1775(1), 92-102.
[PMID: 17014965] 
[17] 
Kalin, T.V.; Ustiyan, V.; Kalinichenko, V.V. Multiple faces of FoxM1 transcription factor: lessons from transgenic mouse models. Cell Cycle,  2011, 10(3), 396-405.
[http://dx.doi.org/10.4161/cc.10.3.14709] [PMID: 21270518] 
[18] 
Huang, B.T.; Lai, W.Y.; Chang, Y.C.; Wang, J.W.; Yeh, S.D.; Lin, E.P.; Yang, P.C.A. CTLA-4 Antagonizing DNA aptamer with antitumor effect. Mol. Ther. Nucleic Acids,  2017, 8, 520-528.
[http://dx.doi.org/10.1016/j.omtn.2017.08.006] [PMID: 28918052] 
[19] 
Lai, W.Y.; Huang, B.T.; Wang, J.W.; Lin, P.Y.; Yang, P.C. A novel PD-L1-targeting antagonistic DNA aptamer with antitumor effects. Mol. Ther. Nucleic Acids,  2016, 5(12)e397
[http://dx.doi.org/10.1038/mtna.2016.102] [PMID: 27959341] 
[20] 
Subramanian, N.; Srimany, A.; Kanwar, J.R.; Kanwar, R.K.; Akilandeswari, B.; Rishi, P.; Khetan, V.; Vasudevan, M.; Pradeep, T.; Krishnakumar, S. Nucleolin-aptamer therapy in retinoblastoma: molecular changes and mass spectrometry-based imaging. Mol. Ther. Nucleic Acids,  2016, 5(8)e358
[http://dx.doi.org/10.1038/mtna.2016.70] [PMID: 27574784] 
[21] 
Zheng, J.; Zhao, S.; Yu, X.; Huang, S.; Liu, H.Y. Simultaneous targeting of CD44 and EpCAM with a bispecific aptamer effectively inhibits intraperitoneal ovarian cancer growth. Theranostics,  2017, 7(5), 1373-1388.
[http://dx.doi.org/10.7150/thno.17826] [PMID: 28435472] 
[22] 
Zhu, G.; Zheng, J.; Song, E.; Donovan, M.; Zhang, K.; Liu, C.; Tan, W. Self-assembled, aptamer-tethered DNA nanotrains for targeted transport of molecular drugs in cancer theranostics. Proc. Natl. Acad. Sci. USA,  2013, 110(20), 7998-8003.
[http://dx.doi.org/10.1073/pnas.1220817110] [PMID: 23630258] 
[23] 
Yu, G.; Li, H.; Yang, S.; Wen, J.; Niu, J.; Zu, Y. ssDNA Aptamer Specifically Targets and Selectively Delivers Cytotoxic Drug Doxorubicin to HepG2 Cells. PLoS One,  2016, 11(1)e0147674
[http://dx.doi.org/10.1371/journal.pone.0147674] [PMID: 26808385] 
[24] 
Xiang, D.; Shigdar, S.; Bean, A.G.; Bruce, M.; Yang, W.; Mathesh, M.; Wang, T.; Yin, W.; Tran, P.H.; Al Shamaileh, H.; Barrero, R.A.; Zhang, P.Z.; Li, Y.; Kong, L.; Liu, K.; Zhou, S.F.; Hou, Y.; He, A.; Duan, W. Transforming doxorubicin into a cancer stem cell killer via EpCAM aptamer-mediated delivery. Theranostics,  2017, 7(17), 4071-4086.
[http://dx.doi.org/10.7150/thno.20168] [PMID: 29158811] 
[25] 
Yazdian-Robati, R.; Ramezani, M.; Jalalian, S.H.; Abnous, K.; Taghdisi, S.M. Targeted Delivery of Epirubicin to Cancer Cells by Polyvalent Aptamer System in vitro and in vivo. Pharm. Res.,  2016, 33(9), 2289-2297.
[http://dx.doi.org/10.1007/s11095-016-1967-4] [PMID: 27283831] 
[26] 
Zhang, Z.; Ali, M.M.; Eckert, M.A.; Kang, D.K.; Chen, Y.Y.; Sender, L.S.; Fruman, D.A.; Zhao, W. A polyvalent aptamer system for targeted drug delivery. Biomaterials,  2013, 34(37), 9728-9735.
[http://dx.doi.org/10.1016/j.biomaterials.2013.08.079] [PMID: 24044994] 
[27] 
Cerchia, L.; Esposito, C.L.; Camorani, S.; Rienzo, A.; Stasio, L.; Insabato, L.; Affuso, A.; de Franciscis, V. Targeting Axl with an high-affinity inhibitory aptamer. Mol. Ther.,  2012, 20(12), 2291-2303.
[http://dx.doi.org/10.1038/mt.2012.163] [PMID: 22910292] 
[28] 
Camorani, S.; Esposito, C.L.; Rienzo, A.; Catuogno, S.; Iaboni, M.; Condorelli, G.; de Franciscis, V.; Cerchia, L. Inhibition of receptor signaling and of glioblastoma-derived tumor growth by a novel PDGFRβ aptamer. Mol. Ther.,  2014, 22(4), 828-841.
[http://dx.doi.org/10.1038/mt.2013.300] [PMID: 24566984] 
[29] 
 Esposito, C.L.; Catuogno, S.; de Franciscis, V. Aptamer-
MiRNA conjugates for cancer cell-targeted delivery in:
SiRNA Delivery Methods: Methods and Protocols; Shum,K.; Rossi, J., Eds.; Springer New York: New York, NY,
2016, pp. 197-208.
[http://dx.doi.org/10.1007/978-1-4939-3112-5_16] 
[30] 
Fichtinger-Schepman, A.M.; van der Veer, J.L.; den Hartog, J.H.; Lohman, P.H.; Reedijk, J. Adducts of the antitumor drug cis-diamminedichloroplatinum(II) with DNA: formation, identification, and quantitation. Biochemistry,  1985, 24(3), 707-713.
[http://dx.doi.org/10.1021/bi00324a025] [PMID: 4039603] 
[31] 
Wang, Y.M.; Wu, Z.; Liu, S.J.; Chu, X. Structure-switching aptamer triggering hybridization chain reaction on the cell surface for activatable theranostics. Anal. Chem.,  2015, 87(13), 6470-6474.
[http://dx.doi.org/10.1021/acs.analchem.5b01634] [PMID: 26044187] 
[32] 
Subramanian, N.; Kanwar, J.R.; Kanwar, R.K.; Krishnakumar, S. Targeting cancer cells using LNA-modified aptamer-siRNA chimeras. Nucleic Acid Ther.,  2015, 25(6), 317-322.
[http://dx.doi.org/10.1089/nat.2015.0550] [PMID: 26334953] 
[33] 
Subramanian, N.; Kanwar, J.R.; Akilandeswari, B.; Kanwar, R.K.; Khetan, V.; Krishnakumar, S. Chimeric nucleolin aptamer with survivin DNAzyme for cancer cell targeted delivery. Chem. Commun. (Camb.),  2015, 51(32), 6940-6943.
[http://dx.doi.org/10.1039/C5CC00939A] [PMID: 25797393] 
[34] 
Yoon, S.; Huang, K.W.; Reebye, V.; Mintz, P.; Tien, Y.W.; Lai, H.S.; Sætrom, P.; Reccia, I.; Swiderski, P.; Armstrong, B.; Jozwiak, A.; Spalding, D.; Jiao, L.; Habib, N.; Rossi, J.J. Targeted delivery of C/EBPα -saRNA by pancreatic ductal adenocarcinoma-specific RNA aptamers inhibits tumor growth in vivo. Mol. Ther.,  2016, 24(6), 1106-1116.
[http://dx.doi.org/10.1038/mt.2016.60] [PMID: 26983359] 
[35] 
Yoon, S.; Huang, K.W.; Reebye, V.; Spalding, D.; Przytycka, T.M.; Wang, Y.; Swiderski, P.; Li, L.; Armstrong, B.; Reccia, I.; Zacharoulis, D.; Dimas, K.; Kusano, T.; Shively, J.; Habib, N.; Rossi, J.J. Aptamer-drug conjugates of active metabolites of nucleoside analogs and cytotoxic agents inhibit pancreatic tumor cell growth. Mol. Ther. Nucleic Acids,  2017, 6, 80-88.
[http://dx.doi.org/10.1016/j.omtn.2016.11.008] [PMID: 28325302] 
[36] 
Wang, R.; Zhu, G.; Mei, L.; Xie, Y.; Ma, H.; Ye, M.; Qing, F.L.; Tan, W. Automated modular synthesis of aptamer-drug conjugates for targeted drug delivery. J. Am. Chem. Soc.,  2014, 136(7), 2731-2734.
[http://dx.doi.org/10.1021/ja4117395] [PMID: 24483627] 
[37] 
Li, F.; Lu, J.; Liu, J.; Liang, C.; Wang, M.; Wang, L.; Li, D.; Yao, H.; Zhang, Q.; Wen, J.; Zhang, Z-K.; Li, J.; Lv, Q.; He, X.; Guo, B.; Guan, D.; Yu, Y.; Dang, L.; Wu, X.; Li, Y.; Chen, G.; Jiang, F.; Sun, S.; Zhang, B-T.; Lu, A.; Zhang, G. A water-soluble nucleolin aptamer-paclitaxel conjugate for tumor-specific targeting in ovarian cancer. Nat. Commun.,  2017, 8(1), 1390.
[http://dx.doi.org/10.1038/s41467-017-01565-6] [PMID: 29123088] 
[38] 
Liu, H.Y.; Yu, X.; Liu, H.; Wu, D.; She, J.X. Co-targeting EGFR and survivin with a bivalent aptamer-dual siRNA chimera effectively suppresses prostate cancer. Sci. Rep.,  2016, 6, 30346.
[http://dx.doi.org/10.1038/srep30346] [PMID: 27456457] 
[39] 
Baek, D.; Villén, J.; Shin, C.; Camargo, F.D.; Gygi, S.P.; Bartel, D.P. The impact of microRNAs on protein output. Nature,  2008, 455(7209), 64-71.
[http://dx.doi.org/10.1038/nature07242] [PMID: 18668037] 
[40] 
AlShamaileh, H.; Wang, T.; Xiang, D.; Yin, W.; Tran, P.H.; Barrero, R.A.; Zhang, P.Z.; Li, Y.; Kong, L.; Liu, K.; Zhou, S.F.; Hou, Y.; Shigdar, S.; Duan, W. Aptamer-mediated survivin RNAi enables 5-fluorouracil to eliminate colorectal cancer stem cells. Sci. Rep.,  2017, 7(1), 5898.
[http://dx.doi.org/10.1038/s41598-017-05859-z] [PMID: 28724889] 
[41] 
Ara, M.N.; Hyodo, M.; Ohga, N.; Hida, K.; Harashima, H. Development of a novel DNA aptamer ligand targeting to primary cultured tumor endothelial cells by a cell-based SELEX method. PLoS One,  2012, 7(12)e50174
[http://dx.doi.org/10.1371/journal.pone.0050174] [PMID: 23226512] 
[42] 
Ara, M.N.; Matsuda, T.; Hyodo, M.; Sakurai, Y.; Hatakeyama, H.; Ohga, N.; Hida, K.; Harashima, H. An aptamer ligand based liposomal nanocarrier system that targets tumor endothelial cells. Biomaterials,  2014, 35(25), 7110-7120.
[http://dx.doi.org/10.1016/j.biomaterials.2014.04.087] [PMID: 24875764] 
[43] 
Zhang, K.; Liu, M.; Tong, X.; Sun, N.; Zhou, L.; Cao, Y.; Wang, J.; Zhang, H.; Pei, R. Aptamer-modified temperature-sensitive liposomal contrast agent for magnetic resonance imaging. Biomacromolecules,  2015, 16(9), 2618-2623.
[http://dx.doi.org/10.1021/acs.biomac.5b00250] [PMID: 26212580] 
[44] 
Zhang, L.X.; Li, K.F.; Wang, H.; Gu, M.J.; Liu, L.S.; Zheng, Z.Z.; Han, N.Y.; Yang, Z.J.; Fan, T.Y. Preparation and in vitro evaluation of a MRI contrast agent based on aptamer-modified gadolinium-loaded liposomes for tumor targeting. AAPS PharmSciTech,  2017, 18(5), 1564-1571.
[http://dx.doi.org/10.1208/s12249-016-0600-5] [PMID: 27604884] 
[45] 
Shrivastava, G.; Hyodo, M.; Yoshimura, S.H.; Akita, H.; Harashima, H. Identification of a nucleoporin358-specific RNA aptamer for use as a nucleus-targeting liposomal delivery system. Nucleic Acid Ther.,  2016, 26(5), 286-298.
[http://dx.doi.org/10.1089/nat.2016.0604] [PMID: 27548508] 
[46] 
Baek, S.E.; Lee, K.H.; Park, Y.S.; Oh, D.K.; Oh, S.; Kim, K.S.; Kim, D.E. RNA aptamer-conjugated liposome as an efficient anticancer drug delivery vehicle targeting cancer cells in vivo. J. Control. Release,  2014, 196, 234-242.
[http://dx.doi.org/10.1016/j.jconrel.2014.10.018] [PMID: 25450401] 
[47] 
Xing, H.; Tang, L.; Yang, X.; Hwang, K.; Wang, W.; Yin, Q.; Wong, N.Y.; Dobrucki, L.W.; Yasui, N.; Katzenellenbogen, J.A.; Helferich, W.G.; Cheng, J.; Lu, Y. Selective delivery of an anticancer drug with aptamer-functionalized liposomes to breast cancer cells in vitro and in vivo. J. Mater. Chem. B Mater. Biol. Med.,  2013, 1(39), 5288-5297.
[http://dx.doi.org/10.1039/c3tb20412j] [PMID: 24159374] 
[48] 
Alshaer, W.; Hillaireau, H.; Vergnaud, J.; Ismail, S.; Fattal, E. Functionalizing liposomes with anti-CD44 aptamer for selective targeting of cancer cells. Bioconjug. Chem.,  2015, 26(7), 1307-1313.
[http://dx.doi.org/10.1021/bc5004313] [PMID: 25343502] 
[49] 
Xing, H.; Li, J.; Xu, W.; Hwang, K.; Wu, P.; Yin, Q.; Li, Z.; Cheng, J.; Lu, Y. The effects of spacer length and composition on aptamer-mediated cell-specific targeting with nanoscale PEGylated liposomal doxorubicin. ChemBioChem,  2016, 17(12), 1111-1117.
[http://dx.doi.org/10.1002/cbic.201600092] [PMID: 27123758] 
[50] 
Li, L.; Hou, J.; Liu, X.; Guo, Y.; Wu, Y.; Zhang, L.; Yang, Z. Nucleolin-targeting liposomes guided by aptamer AS1411 for the delivery of siRNA for the treatment of malignant melanomas. Biomaterials,  2014, 35(12), 3840-3850.
[http://dx.doi.org/10.1016/j.biomaterials.2014.01.019] [PMID: 24486214] 
[51] 
Moosavian, S.A.; Abnous, K.; Badiee, A.; Jaafari, M.R. Improvement in the drug delivery and anti-tumor efficacy of PEGylated liposomal doxorubicin by targeting RNA aptamers in mice bearing breast tumor model. Colloids Surf. B Biointerfaces,  2016, 139, 228-236.
[http://dx.doi.org/10.1016/j.colsurfb.2015.12.009] [PMID: 26722819] 
[52] 
Yamada, Y.; Furukawa, R.; Harashima, H. A dual-ligand liposomal system composed of a cell-penetrating peptide and a mitochondrial RNA aptamer synergistically facilitates cellular uptake and mitochondrial targeting. J. Pharm. Sci.,  2016, 105(5), 1705-1713.
[http://dx.doi.org/10.1016/j.xphs.2016.03.002] [PMID: 27056631] 
[53] 
Chuang, E.Y.; Lin, C.C.; Chen, K.J.; Wan, D.H.; Lin, K.J.; Ho, Y.C.; Lin, P.Y.; Sung, H.W. A FRET-guided, NIR-responsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release. Biomaterials,  2016, 93, 48-59.
[http://dx.doi.org/10.1016/j.biomaterials.2016.03.040] [PMID: 27070992] 
[54] 
Mo, R.; Jiang, T.; Gu, Z. Enhanced anticancer efficacy by ATP-mediated liposomal drug delivery. Angew. Chem. Int. Ed. Engl.,  2014, 53(23), 5815-5820.
[http://dx.doi.org/10.1002/anie.201400268] [PMID: 24764317] 
[55] 
Zhen, S.; Takahashi, Y.; Narita, S.; Yang, Y.C.; Li, X. Targeted delivery of CRISPR/Cas9 to prostate cancer by modified gRNA using a flexible aptamer-cationic liposome. Oncotarget,  2017, 8(6), 9375-9387.
[http://dx.doi.org/10.18632/oncotarget.14072] [PMID: 28030843] 
[56] 
Gabizon, A.; Papahadjopoulos, D. Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors. Proc. Natl. Acad. Sci. USA,  1988, 85(18), 6949-6953.
[http://dx.doi.org/10.1073/pnas.85.18.6949] [PMID: 3413128] 
[57] 
Zhou, W.; Gao, X.; Liu, D.; Chen, X. Gold nanoparticles for in vitro diagnostics. Chem. Rev.,  2015, 115(19), 10575-10636.
[http://dx.doi.org/10.1021/acs.chemrev.5b00100] [PMID: 26114396] 
[58] 
Saha, K.; Agasti, S.S.; Kim, C.; Li, X.; Rotello, V.M. Gold nanoparticles in chemical and biological sensing. Chem. Rev.,  2012, 112(5), 2739-2779.
[http://dx.doi.org/10.1021/cr2001178] [PMID: 22295941] 
[59] 
Ryou, S.M.; Yeom, J.H.; Kang, H.J.; Won, M.; Kim, J.S.; Lee, B.; Seong, M.J.; Ha, N.C.; Bae, J.; Lee, K. Gold nanoparticle-DNA aptamer composites as a universal carrier for in vivo delivery of biologically functional proteins. J. Control. Release,  2014, 196(196), 287-294.
[http://dx.doi.org/10.1016/j.jconrel.2014.10.021] [PMID: 25450403] 
[60] 
Danesh, N.M.; Lavaee, P.; Ramezani, M.; Abnous, K.; Taghdisi, S.M. Targeted and controlled release delivery of daunorubicin to T-cell acute lymphoblastic leukemia by aptamer-modified gold nanoparticles. Int. J. Pharm.,  2015, 489(1-2), 311-317.
[http://dx.doi.org/10.1016/j.ijpharm.2015.04.072] [PMID: 25936625] 
[61] 
Du, Y.Q.; Yang, X.X.; Li, W.L.; Wang, J.; Huang, C.Z. A cancer-targeted drug delivery system developed with gold nanoparticle mediated DNA-doxorubicin conjugates. RSC Advances,  2014, 4(66), 34830-34835.
[http://dx.doi.org/10.1039/C4RA06298A] 
[62] 
Liang, H.; Zhang, X.B.; Lv, Y.; Gong, L.; Wang, R.; Zhu, X.; Yang, R.; Tan, W. Functional DNA-containing nanomaterials: cellular applications in biosensing, imaging, and targeted therapy. Acc. Chem. Res.,  2014, 47(6), 1891-1901.
[http://dx.doi.org/10.1021/ar500078f] [PMID: 24780000] 
[63] 
Niu, W.; Chen, X.; Tan, W.; Veige, A.S. N-heterocyclic carbene-gold(I) complexes conjugated to a leukemia-specific DNA aptamer for targeted drug delivery. Angew. Chem. Int. Ed. Engl.,  2016, 55(31), 8889-8893.
[http://dx.doi.org/10.1002/anie.201602702] [PMID: 27311814] 
[64] 
Wang, X.W.; Gao, W.; Fan, H.; Ding, D.; Lai, X.F.; Zou, Y.X.; Chen, L.; Chen, Z.; Tan, W. Simultaneous tracking of drug molecules and carriers using aptamer-functionalized fluorescent superstable gold nanorod-carbon nanocapsules during thermo-chemotherapy. Nanoscale,  2016, 8(15), 7942-7948.
[http://dx.doi.org/10.1039/C6NR00369A] [PMID: 27004915] 
[65] 
Zhang, P.; Wang, C.; Zhao, J.; Xiao, A.; Shen, Q.; Li, L.; Li, J.; Zhang, J.; Min, Q.; Chen, J.; Chen, H.Y.; Zhu, J.J. Near infrared-guided smart nanocarriers for MicroRNA-controlled release of doxorubicin/siRNA with intracellular ATP as fuel. ACS Nano,  2016, 10(3), 3637-3647.
[http://dx.doi.org/10.1021/acsnano.5b08145] [PMID: 26905935] 
[66] 
Latorre, A.; Posch, C.; Garcimartín, Y.; Celli, A.; Sanlorenzo, M.; Vujic, I.; Ma, J.; Zekhtser, M.; Rappersberger, K.; Ortiz-Urda, S.; Somoza, Á. DNA and aptamer stabilized gold nanoparticles for targeted delivery of anticancer therapeutics. Nanoscale,  2014, 6(13), 7436-7442.
[http://dx.doi.org/10.1039/C4NR00019F] [PMID: 24882040] 
[67] 
Zhang, D.; Zheng, A.; Li, J.; Wu, M.; Wu, L.; Wei, Z.; Liao, N.; Zhang, X.; Cai, Z.; Yang, H.; Liu, G.; Liu, X.; Liu, J. Smart Cu(II)-aptamer complexes based gold nanoplatform for tumor micro-environment triggered programmable intracellular prodrug release, photodynamic treatment and aggregation induced photothermal therapy of hepatocellular carcinoma. Theranostics,  2017, 7(1), 164-179.
[http://dx.doi.org/10.7150/thno.17099] [PMID: 28042325] 
[68] 
Patterson, L.H.; McKeown, S.R. AQ4N: a new approach to hypoxia-activated cancer chemotherapy. Br. J. Cancer,  2000, 83(12), 1589-1593.
[http://dx.doi.org/10.1054/bjoc.2000.1564] [PMID: 11104551] 
[69] 
Patterson, L.H.; McKeown, S.R.; Ruparelia, K.; Double, J.A.; Bibby, M.C.; Cole, S.; Stratford, I.J. Enhancement of chemotherapy and radiotherapy of murine tumours by AQ4N, a bioreductively activated anti-tumour agent. Br. J. Cancer,  2000, 82(12), 1984-1990.
[PMID: 10864207] 
[70] 
Kim, Y.; Park, J-H.; Lee, H.; Nam, J-M. How do the size, charge and shape of nanoparticles affect amyloid β aggregation on brain lipid bilayer? Sci. Rep.,  2016, 6, 19548.
[http://dx.doi.org/10.1038/srep19548] [PMID: 26782664] 
[71] 
Jiao, J.; Zou, Q.; Zou, M.H.; Guo, R.M.; Zhu, S.; Zhang, Y. Aptamer-modified PLGA nanoparticle delivery of triplex forming oligonucleotide for targeted prostate cancer therapy. Neoplasma,  2016, 63(4), 569-575.
[http://dx.doi.org/10.4149/neo_2016_410] [PMID: 27268920] 
[72] 
Zhou, W.; Zhou, Y.; Wu, J.; Liu, Z.; Zhao, H.; Liu, J.; Ding, J. Aptamer-nanoparticle bioconjugates enhance intracellular delivery of vinorelbine to breast cancer cells. J. Drug Target.,  2014, 22(1), 57-66.
[http://dx.doi.org/10.3109/1061186X.2013.839683] [PMID: 24156476] 
[73] 
Alibolandi, M.; Ramezani, M.; Abnous, K.; Sadeghi, F.; Atyabi, F.; Asouri, M.; Ahmadi, A.A.; Hadizadeh, F. In vitro and in vivo evaluation of therapy targeting epithelial-cell adhesion-molecule aptamers for non-small cell lung cancer. J. Control. Release,  2015, 209, 88-100.
[http://dx.doi.org/10.1016/j.jconrel.2015.04.026] [PMID: 25912964] 
[74] 
Alibolandi, M.; Ramezani, M.; Sadeghi, F.; Abnous, K.; Hadizadeh, F. Epithelial cell adhesion molecule aptamer conjugated PEG-PLGA nanopolymersomes for targeted delivery of doxorubicin to human breast adenocarcinoma cell line in vitro. Int. J. Pharm.,  2015, 479(1), 241-251.
[http://dx.doi.org/10.1016/j.ijpharm.2014.12.035] [PMID: 25529433] 
[75] 
Pan, M.; Li, W.; Yang, J.; Li, Z.; Zhao, J.; Xiao, Y.; Xing, Y.; Zhang, X.; Ju, W. Plumbagin-loaded aptamer-targeted poly D,L-lactic-co-glycolic acid-b-polyethylene glycol nanoparticles for prostate cancer therapy. Medicine (Baltimore),  2017, 96(30)e7405
[http://dx.doi.org/10.1097/MD.0000000000007405] [PMID: 28746182] 
[76] 
Wu, M.; Wang, Y.; Wang, Y.; Zhang, M.; Luo, Y.; Tang, J.; Wang, Z.; Wang, D.; Hao, L.; Wang, Z. Paclitaxel-loaded and A10-3.2 aptamer-targeted poly(lactide-co-glycolic acid) nanobubbles for ultrasound imaging and therapy of prostate cancer. Int. J. Nanomedicine,  2017, 12, 5313-5330.
[http://dx.doi.org/10.2147/IJN.S136032] [PMID: 28794625] 
[77] 
Sivakumar, B.; Aswathy, R.G.; Nagaoka, Y.; Iwai, S.; Venugopal, K.; Kato, K.; Yoshida, Y.; Maekawa, T.; Kumar, D.N.S. Aptamer conjugated theragnostic multifunctional magnetic nanoparticles as a nanoplatform for pancreatic cancer therapy. RSC Advances,  2013, 3(43), 20579-20598.
[http://dx.doi.org/10.1039/c3ra42645a] 
[78] 
Liu, Z.; Zhao, H.; He, L.; Yao, Y.; Zhou, Y.; Wu, J.; Liu, J.; Ding, J. Aptamer density dependent cellular uptake of lipid-capped polymer nanoparticles for polyvalent targeted delivery of vinorelbine to cancer cells. RSC Advances,  2015, 5(22), 16931-16939.
[http://dx.doi.org/10.1039/C4RA16371K] 
[79] 
Das, M.; Duan, W.; Sahoo, S.K. Multifunctional nanoparticle-EpCAM aptamer bioconjugates: a paradigm for targeted drug delivery and imaging in cancer therapy. Nanomedicine (Lond.),  2015, 11(2), 379-389.
[http://dx.doi.org/10.1016/j.nano.2014.09.002] [PMID: 25240596] 
[80] 
Chen, Z.; Tai, Z.; Gu, F.; Hu, C.; Zhu, Q.; Gao, S. Aptamer-mediated delivery of docetaxel to prostate cancer through polymeric nanoparticles for enhancement of antitumor efficacy. Eur. J. Pharm. Biopharm.,  2016, 107, 130-141.
[http://dx.doi.org/10.1016/j.ejpb.2016.07.007] [PMID: 27393562] 
[81] 
Mir, M.; Ahmed, N.; Rehman, A.U. Recent applications of PLGA based nanostructures in drug delivery. Colloids Surf. B Biointerfaces,  2017, 159, 217-231.
[http://dx.doi.org/10.1016/j.colsurfb.2017.07.038] [PMID: 28797972] 
[82] 
Fredenberg, S.; Wahlgren, M.; Reslow, M.; Axelsson, A. The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems--a review. Int. J. Pharm.,  2011, 415(1-2), 34-52.
[http://dx.doi.org/10.1016/j.ijpharm.2011.05.049] [PMID: 21640806] 
[83] 
Xie, Z.; Su, Y.; Kim, G.B.; Selvi, E.; Ma, C.; Aragon-Sanabria, V.; Hsieh, J-T.; Dong, C.; Yang, J. Immune cell-mediated biodegradable theranostic nanoparticles for melanoma targeting and drug delivery. Small,  2017, 13(10)1603121
[http://dx.doi.org/10.1002/smll.201603121] [PMID: 28026115] 
[84] 
Chen, Y.; Wang, J.; Wang, J.; Wang, L.; Tan, X.; Tu, K.; Tong, X.; Qi, L. Aptamer functionalized cisplatin-albumin nanoparticles for targeted delivery to epidermal growth factor receptor positive cervical cancer. J. Biomed. Nanotechnol.,  2016, 12(4), 656-666.
[http://dx.doi.org/10.1166/jbn.2016.2203] [PMID: 27301192] 
[85] 
Chu, T.C.; Twu, K.Y.; Ellington, A.D.; Levy, M. Aptamer mediated siRNA delivery. Nucleic Acids Res.,  2006, 34(10)e73
[http://dx.doi.org/10.1093/nar/gkl388] [PMID: 16740739] 
[86] 
Huang, F.; You, M.; Chen, T.; Zhu, G.; Liang, H.; Tan, W. Self-assembled hybrid nanoparticles for targeted co-delivery of two drugs into cancer cells. Chem. Commun. (Camb.),  2014, 50(23), 3103-3105.
[http://dx.doi.org/10.1039/c3cc49003c] [PMID: 24516863] 
[87] 
Li, L.; Xiang, D.; Shigdar, S.; Yang, W.; Li, Q.; Lin, J.; Liu, K.; Duan, W. Epithelial cell adhesion molecule aptamer functionalized PLGA-lecithin-curcumin-PEG nanoparticles for targeted drug delivery to human colorectal adenocarcinoma cells. Int. J. Nanomedicine,  2014, 9(1), 1083-1096.
[PMID: 24591829] 
[88] 
Oh, S.S.; Lee, B.F.; Leibfarth, F.A.; Eisenstein, M.; Robb, M.J.; Lynd, N.A.; Hawker, C.J.; Soh, H.T. Synthetic aptamer-polymer hybrid constructs for programmed drug delivery into specific target cells. J. Am. Chem. Soc.,  2014, 136(42), 15010-15015.
[http://dx.doi.org/10.1021/ja5079464] [PMID: 25290917] 
[89] 
Subramanian, N.; Kanwar, J.R.; Athalya, P.K.; Janakiraman, N.; Khetan, V.; Kanwar, R.K.; Eluchuri, S.; Krishnakumar, S. EpCAM aptamer mediated cancer cell specific delivery of EpCAM siRNA using polymeric nanocomplex. J. Biomed. Sci.,  2015, 22(1), 4.
[http://dx.doi.org/10.1186/s12929-014-0108-9] [PMID: 25576037] 
[90] 
Wang, Z.; Xia, J.; Cai, F.; Zhang, F.; Yang, M.; Bi, S.; Gui, R.; Li, Y.; Xia, Y. Aptamer-functionalized hydrogel as effective anti-cancer drugs delivery agents. Colloids Surf. B Biointerfaces,  2015, 134(20), 40-46.
[http://dx.doi.org/10.1016/j.colsurfb.2015.06.031] [PMID: 26142627] 
[91] 
Xu, G.; Yu, X.; Zhang, J.; Sheng, Y.; Liu, G.; Tao, W.; Mei, L. Robust aptamer-polydopamine-functionalized M-PLGA-TPGS nanoparticles for targeted delivery of docetaxel and enhanced cervical cancer therapy. Int. J. Nanomedicine,  2016, 11, 2953-2965.
[PMID: 27382282] 
[92] 
Zhuang, Y.; Deng, H.; Su, Y.; He, L.; Wang, R.; Tong, G.; He, D.; Zhu, X. aptamer-functionalized and backbone redox-responsive hyperbranched polymer for targeted drug delivery in cancer therapy. Biomacromolecules,  2016, 17(6), 2050-2062.
[http://dx.doi.org/10.1021/acs.biomac.6b00262] [PMID: 27113017] 
[93] 
Li, X.; Zhu, X.; Qiu, L. Constructing aptamer anchored nanovesicles for enhanced tumor penetration and cellular uptake of water soluble chemotherapeutics. Acta Biomater.,  2016, 35, 269-279.
[http://dx.doi.org/10.1016/j.actbio.2016.02.012] [PMID: 26873366] 
[94] 
Wang, C.; Liu, B.; Xu, X.; Zhuang, B.; Li, H.; Yin, J.; Cong, M.; Xu, W.; Lu, A. Toward targeted therapy in chemotherapy-resistant pancreatic cancer with a smart triptolide nanomedicine. Oncotarget,  2016, 7(7), 8360-8372.
[http://dx.doi.org/10.18632/oncotarget.7073] [PMID: 26840019] 
[95] 
Song, X.; Ren, Y.; Zhang, J.; Wang, G.; Han, X.; Zheng, W.; Zhen, L. Targeted delivery of doxorubicin to breast cancer cells by aptamer functionalized DOTAP/DOPE liposomes. Oncol. Rep.,  2015, 34(4), 1953-1960.
[http://dx.doi.org/10.3892/or.2015.4136] [PMID: 26238192] 
[96] 
Seleci, D.A.; Seleci, M.; Jochums, A.; Walter, J.G.; Stahl, F.; Scheper, T. Aptamer mediated niosomal drug delivery. RSC Advances,  2016, 6(91), 87910-87918.
[http://dx.doi.org/10.1039/C6RA19525C] 
[97] 
Varnamkhasti, B.S.; Hosseinzadeh, H.; Azhdarzadeh, M.; Vafaei, S.Y.; Esfandyari-Manesh, M.; Mirzaie, Z.H.; Amini, M.; Ostad, S.N.; Atyabi, F.; Dinarvand, R. Protein corona hampers targeting potential of MUC1 aptamer functionalized SN-38 core-shell nanoparticles. Int. J. Pharm.,  2015, 494(1), 430-444.
[http://dx.doi.org/10.1016/j.ijpharm.2015.08.060] [PMID: 26315125] 
[98] 
Sayari, E.; Dinarvand, M.; Amini, M.; Azhdarzadeh, M.; Mollarazi, E.; Ghasemi, Z.; Atyabi, F. MUC1 aptamer conjugated to chitosan nanoparticles, an efficient targeted carrier designed for anticancer SN38 delivery. Int. J. Pharm.,  2014, 473(1-2), 304-315.
[http://dx.doi.org/10.1016/j.ijpharm.2014.05.041] [PMID: 24905777] 
[99] 
Ghasemi, Z.; Dinarvand, R.; Mottaghitalab, F.; Esfandyari-Manesh, M.; Sayari, E.; Atyabi, F. Aptamer decorated hyaluronan/chitosan nanoparticles for targeted delivery of 5-fluorouracil to MUC1 overexpressing adenocarcinomas. Carbohydr. Polym.,  2015, 121, 190-198.
[http://dx.doi.org/10.1016/j.carbpol.2014.12.025] [PMID: 25659689] 
[100] 
Atabi, F.; Mousavi Gargari, S.L.; Hashemi, M.; Yaghmaei, P. Doxorubicin loaded dna aptamer linked myristilated chitosan nanogel for targeted drug delivery to prostate cancer. Iran. J. Pharm. Res.,  2017, 16(1), 35-49.
[PMID: 28496460] 
[101] 
Roy, K.; Kanwar, R.K.; Cheung, C.H.A.; Fleming, C.L.; Veedu, R.N.; Krishnakumar, S.; Kanwar, J.R. Locked nucleic acid modified bi-specific aptamer-targeted nanoparticles carrying survivin antagonist towards effective colon cancer therapy. Biomicrofluidics,  2015, 5(5), 29008-29016.
[http://dx.doi.org/10.1039/C5RA03791C] 
[102] 
Elgadir, M.A.; Uddin, M.S.; Ferdosh, S.; Adam, A.; Chowdhury, A.J.K.; Sarker, M.Z.I. Impact of chitosan composites and chitosan nanoparticle composites on various drug delivery systems: A review. Yao Wu Shi Pin Fen Xi,  2015, 23(4), 619-629.
[http://dx.doi.org/10.1016/j.jfda.2014.10.008] [PMID: 28911477] 
[103] 
Jang, D.; Lee, Y.M.; Lee, J.; Doh, J.; Kim, W.J. Remission of lymphoblastic leukaemia in an intravascular fluidic environment by pliable drug carrier with a sliding target ligand. Sci. Rep.,  2017, 7, 40739.
[http://dx.doi.org/10.1038/srep40739] [PMID: 28094326] 
[104] 
Guéron, M.; Leroy, J-L. The i-motif in nucleic acids. Curr. Opin. Struct. Biol.,  2000, 10(3), 326-331.
[http://dx.doi.org/10.1016/S0959-440X(00)00091-9] [PMID: 10851195] 
[105] 
Choi, J.; Kim, S.; Tachikawa, T.; Fujitsuka, M.; Majima, T. pH-induced intramolecular folding dynamics of i-motif DNA. J. Am. Chem. Soc.,  2011, 133(40), 16146-16153.
[http://dx.doi.org/10.1021/ja2061984] [PMID: 21882887] 
[106] 
Kato, K.; Yasuda, T.; Ito, K. Viscoelastic properties of slide-ring gels reflecting sliding dynamics of partial chains and entropy of ring components. Macromolecules,  2012, 46(1), 310-316.
[http://dx.doi.org/10.1021/ma3021135] 
[107] 
Lin, L.; Dong, M.; Liu, C.; Wei, C.; Wang, Y.; Sun, H.; Ye, H. A supramolecular strategy for self-mobile adsorption sites in affinity membrane. Macromol. Rapid Commun.,  2014, 35(18), 1587-1591.
[http://dx.doi.org/10.1002/marc.201400289] [PMID: 25074320] 
[108] 
Wang, Y.; Chen, X.; Tian, B.; Liu, J.; Yang, L.; Zeng, L.; Chen, T.; Hong, A.; Wang, X. Nucleolin-targeted extracellular vesicles as a versatile platform for biologics delivery to breast cancer. Theranostics,  2017, 7(5), 1360-1372.
[http://dx.doi.org/10.7150/thno.16532] [PMID: 28435471] 
[109] 
Pi, F.; Binzel, D.W.; Lee, T.J.; Li, Z.; Sun, M.; Rychahou, P.; Li, H.; Haque, F.; Wang, S.; Croce, C.M.; Guo, B.; Evers, B.M.; Guo, P. Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression. Nat. Nanotechnol.,  2018, 13(1), 82-89.
[http://dx.doi.org/10.1038/s41565-017-0012-z] [PMID: 29230043] 
[110] 
Liu, Y.; Wu, X.; Gao, Y.; Zhang, J.; Zhang, D.; Gu, S.; Zhu, G.; Liu, G.; Li, X. Aptamer-functionalized peptide H3CR5C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma. Int. J. Nanomedicine,  2016, 11, 3891-3905.
[http://dx.doi.org/10.2147/IJN.S108128] [PMID: 27574422] 
[111] 
Wang, H.; Zhao, X.; Guo, C.; Ren, D.; Zhao, Y.; Xiao, W.; Jiao, W. Aptamer-dendrimer bioconjugates for targeted delivery of mir-34a expressing plasmid and antitumor effects in non-small cell lung cancer cells. PLoS One,  2015, 10(9)e0139136
[http://dx.doi.org/10.1371/journal.pone.0139136] [PMID: 26406332] 
[112] 
Mohammadzadeh, P.; Cohan, R.A.; Ghoreishi, S.M.; Bitarafan-Rajabi, A.; Ardestani, M.S. AS1411 Aptamer-anionic linear globular dendrimer G2-iohexol selective nano-theranostics. Sci. Rep.,  2017, 7(1), 11832.
[http://dx.doi.org/10.1038/s41598-017-12150-8] [PMID: 28928437] 
[113] 
Chen, Y.; Zhang, H.; Cai, X.; Ji, J.; He, S.; Zhai, G. Multifunctional mesoporous silica nanocarriers for stimuli-responsive target delivery of anticancer drugs. RSC Advances,  2016, 6(94), 92073-92091.
[http://dx.doi.org/10.1039/C6RA18062K] 
[114] 
Xie, X.; Li, F.; Zhang, H.; Lu, Y.; Lian, S.; Lin, H.; Gao, Y.; Jia, L. EpCAM aptamer-functionalized mesoporous silica nanoparticles for efficient colon cancer cell-targeted drug delivery. Eur. J. Pharm. Sci.,  2016, 83, 28-35.
[http://dx.doi.org/10.1016/j.ejps.2015.12.014] [PMID: 26690044] 
[115] 
Wang, K.; Yao, H.; Meng, Y.; Wang, Y.; Yan, X.; Huang, R. Specific aptamer-conjugated mesoporous silica-carbon nanoparticles for HER2-targeted chemo-photothermal combined therapy. Acta Biomater.,  2015, 16, 196-205.
[http://dx.doi.org/10.1016/j.actbio.2015.01.002] [PMID: 25596325] 
[116] 
Zhang, Y.; Hou, Z.; Ge, Y.; Deng, K.; Liu, B.; Li, X.; Li, Q.; Cheng, Z.; Ma, P.; Li, C.; Lin, J. DNA-hybrid-gated photothermal mesoporous silica nanoparticles for NIR-responsive and aptamer-targeted drug delivery. ACS Appl. Mater. Interfaces,  2015, 7(37), 20696-20706.
[http://dx.doi.org/10.1021/acsami.5b05522] [PMID: 26325285] 
[117] 
Ju, E.; Li, Z.; Liu, Z.; Ren, J.; Qu, X. Near-infrared light-triggered drug-delivery vehicle for mitochondria-targeted chemo-photothermal therapy. ACS Appl. Mater. Interfaces,  2014, 6(6), 4364-4370.
[http://dx.doi.org/10.1021/am5000883] [PMID: 24559457] 
[118] 
Tang, Y.; Hu, H.; Zhang, M.G.; Song, J.; Nie, L.; Wang, S.; Niu, G.; Huang, P.; Lu, G.; Chen, X. An aptamer-targeting photoresponsive drug delivery system using “off-on” graphene oxide wrapped mesoporous silica nanoparticles. Nanoscale,  2015, 7(14), 6304-6310.
[http://dx.doi.org/10.1039/C4NR07493A] [PMID: 25782595] 
[119] 
Zhang, P.; Cheng, F.; Zhou, R.; Cao, J.; Li, J.; Burda, C.; Min, Q.; Zhu, J-J. DNA-hybrid-gated multifunctional mesoporous silica nanocarriers for dual-targeted and microRNA-responsive controlled drug delivery. Angew. Chem. Int. Ed. Engl.,  2014, 53(9), 2371-2375.
[http://dx.doi.org/10.1002/anie.201308920] [PMID: 24470397] 
[120] 
Li, Y.; Duo, Y.; Bao, S.; He, L.; Ling, K.; Luo, J.; Zhang, Y.; Huang, H.; Zhang, H.; Yu, X. EpCAM aptamer-functionalized polydopamine-coated mesoporous silica nanoparticles loaded with DM1 for targeted therapy in colorectal cancer. Int. J. Nanomedicine,  2017, 12, 6239-6257.
[http://dx.doi.org/10.2147/IJN.S143293] [PMID: 28894364] 
[121] 
Zheng, F.F.; Zhang, P.H.; Xi, Y.; Chen, J.J.; Li, L.L.; Zhu, J.J. Aptamer/graphene quantum dots nanocomposite capped fluorescent mesoporous silica nanoparticles for intracellular drug delivery and real-time monitoring of drug release. Anal. Chem.,  2015, 87(23), 11739-11745.
[http://dx.doi.org/10.1021/acs.analchem.5b03131] [PMID: 26524192] 
[122] 
Slowing, I.I.; Vivero-Escoto, J.L.; Wu, C.W.; Lin, V.S. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv. Drug Deliv. Rev.,  2008, 60(11), 1278-1288.
[http://dx.doi.org/10.1016/j.addr.2008.03.012] [PMID: 18514969] 
[123] 
Fan, Z.; Li, S.; Yuan, F.; Fan, L. Fluorescent graphene quantum dots for biosensing and bioimaging. RSC Advances,  2015, 5(25), 19773-19789.
[http://dx.doi.org/10.1039/C4RA17131D] 
[124] 
Mo, R.; Jiang, T.; Sun, W.; Gu, Z. ATP-responsive DNA-graphene hybrid nanoaggregates for anticancer drug delivery. Biomaterials,  2015, 50(1), 67-74.
[http://dx.doi.org/10.1016/j.biomaterials.2015.01.053] [PMID: 25736497] 
[125] 
Kim, M.G.; Park, J.Y.; Miao, W.; Lee, J.; Oh, Y.K. Polyaptamer DNA nanothread-anchored, reduced graphene oxide nanosheets for targeted delivery. Biomaterials,  2015, 48, 129-136.
[http://dx.doi.org/10.1016/j.biomaterials.2015.01.009] [PMID: 25701038] 
[126] 
Li, H.; Guo, L.; Huang, A.; Xu, H.; Liu, X.; Ding, H.; Dong, J.; Li, J.; Wang, C.; Su, X.; Ge, X.; Sun, L.; Bai, C.; Shen, X.; Fang, T.; Li, Z.; Zhou, Y.; Zhan, L.; Li, S.; Xie, J.; Shao, N. Nanoparticle-conjugated aptamer targeting hnRNP A2/B1 can recognize multiple tumor cells and inhibit their proliferation. Biomaterials,  2015, 63, 168-176.
[http://dx.doi.org/10.1016/j.biomaterials.2015.06.013] [PMID: 26107993] 
[127] 
Zhou, C.; Chen, T.; Wu, C.; Zhu, G.; Qiu, L.; Cui, C.; Hou, W.; Tan, W. Aptamer CaCO3 nanostructures: a facile, pH-responsive, specific platform for targeted anticancer theranostics. Chem. Asian J.,  2015, 10(1), 166-171.
[http://dx.doi.org/10.1002/asia.201403115] [PMID: 25377905] 
[128] 
Liao, W-C.; Lilienthal, S.; Kahn, J.S.; Riutin, M.; Sohn, Y.S.; Nechushtai, R.; Willner, I. pH- and ligand-induced release of loads from DNA-acrylamide hydrogel microcapsules. Chem. Sci. (Camb.),  2017, 8(5), 3362-3373.
[http://dx.doi.org/10.1039/C6SC04770J] [PMID: 28507706] 
[129] 
Li, C.; Qian, M.; Wang, S.; Jiang, H.; Du, Y.; Wang, J.; Lu, W.; Murthy, N.; Huang, R. aptavalve-gated mesoporous carbon nanospheres image cellular mucin and provide on-demand targeted drug delivery. Theranostics,  2017, 7(13), 3319-3325.
[http://dx.doi.org/10.7150/thno.18692] [PMID: 28900512] 
[130] 
 Catuogno, S.; Esposito, C.L.; Condorelli, G.; de Franciscis,
V. Nucleic acids delivering nucleic acids. Advanced Drug
Delivery Reviews, 2018, pii, S0169-409X(18)30058-9.
[http://dx.doi.org/10.1016/j.addr.2018.04.006] 
[131] 
Wu, C.; Han, D.; Chen, T.; Peng, L.; Zhu, G.; You, M.; Qiu, L.; Sefah, K.; Zhang, X.; Tan, W. Building a multifunctional aptamer-based DNA nanoassembly for targeted cancer therapy. J. Am. Chem. Soc.,  2013, 135(49), 18644-18650.
[http://dx.doi.org/10.1021/ja4094617] [PMID: 24245521] 
[132] 
Ni, X.; Zhang, Y.; Zennami, K.; Castanares, M.; Mukherjee, A.; Raval, R.R.; Zhou, H.; DeWeese, T.L.; Lupold, S.E. Systemic administration and targeted radiosensitization via chemically synthetic aptamer-siRNA chimeras in human tumor xenografts. Mol. Cancer Ther.,  2015, 14(12), 2797-2804.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0291-T] [PMID: 26438155] 
[133] 
Meng, H.M.; Zhang, X.; Lv, Y.; Zhao, Z.; Wang, N.N.; Fu, T.; Fan, H.; Liang, H.; Qiu, L.; Zhu, G.; Tan, W. DNA dendrimer: an efficient nanocarrier of functional nucleic acids for intracellular molecular sensing. ACS Nano,  2014, 8(6), 6171-6181.
[http://dx.doi.org/10.1021/nn5015962] [PMID: 24806614] 
[134] 
Taghdisi, S.M.; Danesh, N.M.; Ramezani, M.; Lavaee, P.; Jalalian, S.H.; Robati, R.Y.; Abnous, K. Double targeting and aptamer-assisted controlled release delivery of epirubicin to cancer cells by aptamers-based dendrimer in vitro and in vivo. Eur. J. Pharm. Biopharm.,  2016, 102, 152-158.
[http://dx.doi.org/10.1016/j.ejpb.2016.03.013] [PMID: 26987703] 
[135] 
Zhang, H.; Ma, Y.; Xie, Y.; An, Y.; Huang, Y.; Zhu, Z.; Yang, C.J. A controllable aptamer-based self-assembled DNA dendrimer for high affinity targeting, bioimaging and drug delivery. Sci. Rep.,  2015, 5, 10099.
[http://dx.doi.org/10.1038/srep10099] [PMID: 25959874] 
[136] 
Sun, P.; Zhang, N.; Tang, Y.; Yang, Y.; Chu, X.; Zhao, Y. SL2B aptamer and folic acid dual-targeting DNA nanostructures for synergic biological effect with chemotherapy to combat colorectal cancer. Int. J. Nanomedicine,  2017, 12, 2657-2672.
[http://dx.doi.org/10.2147/IJN.S132929] [PMID: 28435250] 
[137] 
Goodman, R.P.; Berry, R.M.; Turberfield, A.J. The single-step synthesis of a DNA tetrahedron. Chem. Commun. (Camb.),  2004, (12), 1372-1373.
[http://dx.doi.org/10.1039/b402293a] [PMID: 15179470] 
[138] 
Chen, H.; Wang, Y.; Yao, Y.; Qiao, S.; Wang, H.; Tan, N. Sequential delivery of cyclopeptide RA-V and doxorubicin for combination therapy on resistant tumor and in situ monitoring of cytochrome c release. Theranostics,  2017, 7(15), 3781-3793.
[http://dx.doi.org/10.7150/thno.20892] [PMID: 29109776] 
[139] 
Rin Jean, S.; Tulumello, D.V.; Wisnovsky, S.P.; Lei, E.K.; Pereira, M.P.; Kelley, S.O. Molecular vehicles for mitochondrial chemical biology and drug delivery. ACS Chem. Biol.,  2014, 9(2), 323-333.
[http://dx.doi.org/10.1021/cb400821p] [PMID: 24410267] 
[140] 
Graf, N.; Bielenberg, D.R.; Kolishetti, N.; Muus, C.; Banyard, J.; Farokhzad, O.C.; Lippard, S.J. α(V)β(3) integrin-targeted PLGA-PEG nanoparticles for enhanced anti-tumor efficacy of a Pt(IV) prodrug. ACS Nano,  2012, 6(5), 4530-4539.
[http://dx.doi.org/10.1021/nn301148e] [PMID: 22584163] 
[141] 
Hofman, J.; Buncek, M.; Haluza, R.; Streinz, L.; Ledvina, M.; Cigler, P. In vitro transfection mediated by dendrigraft poly(L-lysines): the effect of structure and molecule size. Macromol. Biosci.,  2013, 13(2), 167-176.
[http://dx.doi.org/10.1002/mabi.201200303] [PMID: 23233456] 
[142] 
Tung, J.; Tew, L.S.; Hsu, Y.M.; Khung, Y.L. A novel 4-arm DNA/RNA nanoconstruct triggering rapid apoptosis of triple negative breast cancer cells within 24 hours. Sci. Rep.,  2017, 7(1), 793.
[http://dx.doi.org/10.1038/s41598-017-00912-3] [PMID: 28400564] 
[143] 
Li, J.; Fan, C.; Pei, H.; Shi, J.; Huang, Q. Smart drug delivery nanocarriers with self-assembled DNA nanostructures. Adv. Mater.,  2013, 25(32), 4386-4396.
[http://dx.doi.org/10.1002/adma.201300875] [PMID: 23765613] 
[144] 
Leach, J.C.; Wang, A.; Ye, K.; Jin, S. A RNA-DNA Hybrid aptamer for nanoparticle-based prostate tumor targeted drug delivery. Int. J. Mol. Sci.,  2016, 17(3), 380.
[http://dx.doi.org/10.3390/ijms17030380] [PMID: 26985893] 
[145] 
Pala, K.; Serwotka, A.; Jeleń, F.; Jakimowicz, P.; Otlewski, J. Tumor-specific hyperthermia with aptamer-tagged superparamagnetic nanoparticles. Int. J. Nanomedicine,  2014, 9, 67-76.
[PMID: 24379664] 
[146] 
Hradil, J.; Pisarev, A.; Babič, M.; Horák, D. Dextran-modified iron oxide nanoparticles. China Particuol.,  2007, 5(1), 162-168.
[http://dx.doi.org/10.1016/j.cpart.2007.01.003] 
[147] 
Jurek, P.M.; Zabłocki, K.; Waśko, U.; Mazurek, M.P.; Otlewski, J.; Jeleń, F. Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy. Int. J. Nanomedicine,  2017, 12, 2941-2950.
[http://dx.doi.org/10.2147/IJN.S125231] [PMID: 28442904] 
[148] 
Laurent, S.; Saei, A.A.; Behzadi, S.; Panahifar, A.; Mahmoudi, M. Superparamagnetic iron oxide nanoparticles for delivery of therapeutic agents: opportunities and challenges. Expert Opin. Drug Deliv.,  2014, 11(9), 1449-1470.
[http://dx.doi.org/10.1517/17425247.2014.924501] [PMID: 24870351] 
[149] 
Han, Z.; Wang, X.; Heng, C.; Han, Q.; Cai, S.; Li, J.; Qi, C.; Liang, W.; Yang, R.; Wang, C. Synergistically enhanced photocatalytic and chemotherapeutic effects of aptamer-functionalized ZnO nanoparticles towards cancer cells. Phys. Chem. Chem. Phys.,  2015, 17(33), 21576-21582.
[http://dx.doi.org/10.1039/C5CP02139A] [PMID: 26220437] 
[150] 
Xiong, H.M. ZnO nanoparticles applied to bioimaging and drug delivery. Adv. Mater.,  2013, 25(37), 5329-5335.
[http://dx.doi.org/10.1002/adma.201301732] [PMID: 24089351] 
[151] 
Peng, L.H.; Zhang, Y.H.; Han, L.J.; Zhang, C.Z.; Wu, J.H.; Wang, X.R.; Gao, J.Q.; Mao, Z.W. Cell membrane capsules for encapsulation of chemotherapeutic and cancer cell targeting in vivo. ACS Appl. Mater. Interfaces,  2015, 7(33), 18628-18637.
[http://dx.doi.org/10.1021/acsami.5b05065] [PMID: 26262951] 
[152] 
Chen, W.H.; Yu, X.; Cecconello, A.; Sohn, Y.S.; Nechushtai, R.; Willner, I. Stimuli-responsive nucleic acid-functionalized metal-organic framework nanoparticles using pH- and metal-ion-dependent DNAzymes as locks. Chem. Sci. (Camb.),  2017, 8(8), 5769-5780.
[http://dx.doi.org/10.1039/C7SC01765K] [PMID: 28989617] 
[153] 
Cai, W.; Chu, C-C.; Liu, G.; Wáng, Y-X.J. Metal-organic framework-based nanomedicine platforms for drug delivery and molecular imaging. Small,  2015, 11(37), 4806-4822.
[http://dx.doi.org/10.1002/smll.201500802] [PMID: 26193176] 
[154] 
Liu, Q.; Jin, C.; Wang, Y.; Fang, X.; Zhang, X.; Chen, Z.; Tan, W. Aptamer-conjugated nanomaterials for specific cancer cell recognition and targeted cancer therapy. NPG Asia Mater.,  2014, 6(4)e95
[http://dx.doi.org/10.1038/am.2014.12] [PMID: 29619132] 
[155] 
Malik, M.T.; O’Toole, M.G.; Casson, L.K.; Thomas, S.D.; Bardi, G.T.; Reyes-Reyes, E.M.; Ng, C.K.; Kang, K.A.; Bates, P.J. AS1411-conjugated gold nanospheres and their potential for breast cancer therapy. Oncotarget,  2015, 6(26), 22270-22281.
[http://dx.doi.org/10.18632/oncotarget.4207] [PMID: 26045302] 
[156] 
Belyanina, I.V.; Zamay, T.N.; Zamay, G.S.; Zamay, S.S.; Kolovskaya, O.S.; Ivanchenko, T.I.; Denisenko, V.V.; Kirichenko, A.K.; Glazyrin, Y.E.; Garanzha, I.V.; Grigorieva, V.V.; Shabanov, A.V.; Veprintsev, D.V.; Sokolov, A.E.; Sadovskii, V.M.; Gargaun, A.; Berezovski, M.V.; Kichkailo, A.S. In vivo cancer cells elimination guided by aptamer-functionalized gold-coated magnetic nanoparticles and controlled with low frequency alternating magnetic field. Theranostics,  2017, 7(13), 3326-3337.
[http://dx.doi.org/10.7150/thno.17089] [PMID: 28900513] 
[157] 
Kolovskaya, O.S.; Zamay, T.N.; Zamay, A.S.; Glazyrin, Y.E.; Spivak, E.A.; Zubkova, O.A.; Kadkina, A.V.; Erkaev, E.N.; Zamay, G.S.; Savitskaya, A.G. DNA-aptamer/protein interaction as a cause of apoptosis and arrest of proliferation in Ehrlich ascites adenocarcinoma cells. Biochemistry (Moscow). Supplement Series A: Membrane and Cell Biology,  2014, 8(1), 60-72.
[http://dx.doi.org/10.1134/S1990747813050061] 
[158] 
Veiseh, O.; Gunn, J.W.; Zhang, M. Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv. Drug Deliv. Rev.,  2010, 62(3), 284-304.
[http://dx.doi.org/10.1016/j.addr.2009.11.002] [PMID: 19909778] 
Rights & Permissions Print Cite
Article Metrics
437
35
2
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0929867325666181008142831	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Aptamer-Based Targeted Drug Delivery Systems: Current Potential and Challenges

Abstract Play Pause

Related Journals

Related Books

Related Articles

Abstract
