Recent Progress of Aptamer‒drug Conjugates in Cancer Therapy

Overview

Journal Acta Pharm Sin B

Publisher Elsevier

Specialty Pharmacology

Date 2023 May 4

PMID 37139427

Authors

Jiaxuan He

Qiao Duan

Chunyan Ran

Ting Fu

Yuan Liu

Weihong Tan

Affiliations

Soon will be listed here.

Abstract

Aptamers are single-stranded DNA or RNA sequences that can specifically bind with the target protein or molecule specific secondary structures. Compared to antibody-drug conjugates (ADC), aptamer‒drug conjugate (ApDC) is also an efficient, targeted drug for cancer therapy with a smaller size, higher chemical stability, lower immunogenicity, faster tissue penetration, and facile engineering. Despite all these advantages, several key factors have delayed the clinical translation of ApDC, such as off-target effects and potential safety issues. In this review, we highlight the most recent progress in the development of ApDC and discuss solutions to the problems noted above.

Citing Articles

Recent Advances in Smart Linkage Strategies for Developing Drug Conjugates for Targeted Delivery.

Zhang J, Yang Z, Liu Y, Liu Y, Qu J, Pan X Top Curr Chem (Cham). 2025; 383(2):13.

PMID: 40080285 DOI: 10.1007/s41061-025-00497-w.

An overview of Sgc8 aptamer as a potential theranostic agent for cancer with PTK7 oncogenic target.

Wang Y, Yuan Z, Zhai L, Lv M, Iqbal H, Ur-Rehman U Sci Prog. 2025; 108(1):368504251325385.

PMID: 40033943 PMC: 11877490. DOI: 10.1177/00368504251325385.

In Silico Born Designed Anti-EGFR Aptamer Gol1 Has Anti-Proliferative Potential for Patient Glioblastoma Cells.

Golovin A, Dzarieva F, Rubetskaya K, Shamadykova D, Usachev D, Pavlova G Int J Mol Sci. 2025; 26(3).

PMID: 39940838 PMC: 11817825. DOI: 10.3390/ijms26031072.

A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer.

Zheng X, Wang Y, Duan H, Hou J, He S J Nanobiotechnology. 2025; 23(1):52.

PMID: 39875991 PMC: 11773979. DOI: 10.1186/s12951-025-03127-1.

A novel shark VNAR antibody-based immunotoxin targeting TROP-2 for cancer therapy.

Xi X, Wang Y, An G, Feng S, Zhu Q, Wu Z Acta Pharm Sin B. 2024; 14(11):4806-4818.

PMID: 39664437 PMC: 11628804. DOI: 10.1016/j.apsb.2024.08.023.

References

Yoon S, Huang K, Reebye V, Spalding D, Przytycka T, Wang Y . 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. PMC: 5363417. DOI: 10.1016/j.omtn.2016.11.008. View

Zhu Y, Tang K, Lv J . Peptide-drug conjugate-based novel molecular drug delivery system in cancer. Trends Pharmacol Sci. 2021; 42(10):857-869. DOI: 10.1016/j.tips.2021.07.001. View

Tarantino P, Carmagnani Pestana R, Corti C, Modi S, Bardia A, Tolaney S . Antibody-drug conjugates: Smart chemotherapy delivery across tumor histologies. CA Cancer J Clin. 2021; 72(2):165-182. DOI: 10.3322/caac.21705. View

Joubert N, Beck A, Dumontet C, Denevault-Sabourin C . Antibody-Drug Conjugates: The Last Decade. Pharmaceuticals (Basel). 2020; 13(9). PMC: 7558467. DOI: 10.3390/ph13090245. View

Li Y, Peng Y, Tan Y, Xuan W, Fu T, Wang X . A new paradigm for artesunate anticancer function: considerably enhancing the cytotoxicity via conjugating artesunate with aptamer. Signal Transduct Target Ther. 2021; 6(1):327. PMC: 8429419. DOI: 10.1038/s41392-021-00671-8. View

Zhang L, Chen C, Fan X, Tang X . Photomodulating Gene Expression by Using Caged siRNAs with Single-Aptamer Modification. Chembiochem. 2018; 19(12):1259-1263. DOI: 10.1002/cbic.201700623. View

Carvalho C, Santos R, Cardoso S, Correia S, Oliveira P, Santos M . Doxorubicin: the good, the bad and the ugly effect. Curr Med Chem. 2009; 16(25):3267-85. DOI: 10.2174/092986709788803312. View

Zang Y, Wei Y, Shi Y, Chen Q, Xing D . Chemo/Photoacoustic Dual Therapy with mRNA-Triggered DOX Release and Photoinduced Shockwave Based on a DNA-Gold Nanoplatform. Small. 2015; 12(6):756-69. DOI: 10.1002/smll.201502857. View

Wen J, Tao W, Hao S, Iyer S, Zu Y . A unique aptamer-drug conjugate for targeted therapy of multiple myeloma. Leukemia. 2015; 30(4):987-91. DOI: 10.1038/leu.2015.216. View

10.

Chau C, Steeg P, Figg W . Antibody-drug conjugates for cancer. Lancet. 2019; 394(10200):793-804. DOI: 10.1016/S0140-6736(19)31774-X. View

11.

Miao Y, Gao Q, Mao M, Zhang C, Yang L, Yang Y . Bispecific Aptamer Chimeras Enable Targeted Protein Degradation on Cell Membranes. Angew Chem Int Ed Engl. 2021; 60(20):11267-11271. DOI: 10.1002/anie.202102170. View

12.

Jain S, Kaur J, Prasad S, Roy I . Nucleic acid therapeutics: a focus on the development of aptamers. Expert Opin Drug Discov. 2020; 16(3):255-274. DOI: 10.1080/17460441.2021.1829587. View

13.

Cho H, Yeh E, Sinha R, Laurence T, Bearinger J, Lee L . Single-step nanoplasmonic VEGF165 aptasensor for early cancer diagnosis. ACS Nano. 2012; 6(9):7607-14. PMC: 3458122. DOI: 10.1021/nn203833d. View

14.

Li W, Yang X, He L, Wang K, Wang Q, Huang J . Self-Assembled DNA Nanocentipede as Multivalent Drug Carrier for Targeted Delivery. ACS Appl Mater Interfaces. 2016; 8(39):25733-25740. DOI: 10.1021/acsami.6b08210. View

15.

Wang Y, Tang L, Li Z, Lin Y, Li J . In situ simultaneous monitoring of ATP and GTP using a graphene oxide nanosheet-based sensing platform in living cells. Nat Protoc. 2014; 9(8):1944-55. DOI: 10.1038/nprot.2014.126. View

16.

Geng Z, Cao Z, Liu R, Liu K, Liu J, Tan W . Aptamer-assisted tumor localization of bacteria for enhanced biotherapy. Nat Commun. 2021; 12(1):6584. PMC: 8593157. DOI: 10.1038/s41467-021-26956-8. View

17.

Huang Z, Wang D, Long C, Li S, Wang X, Tan W . Regulating the Anticancer Efficacy of Sgc8-Combretastatin A4 Conjugates: A Case of Recognizing the Significance of Linker Chemistry for the Design of Aptamer-Based Targeted Drug Delivery Strategies. J Am Chem Soc. 2021; 143(23):8559-8564. DOI: 10.1021/jacs.1c03013. View

18.

Dean A, Luo S, Twomey J, Zhang B . Targeting cancer with antibody-drug conjugates: Promises and challenges. MAbs. 2021; 13(1):1951427. PMC: 8300931. DOI: 10.1080/19420862.2021.1951427. View

19.

Deng Z, Yang Q, Peng Y, He J, Xu S, Wang D . Polymeric Engineering of Aptamer-Drug Conjugates for Targeted Cancer Therapy. Bioconjug Chem. 2019; 31(1):37-42. DOI: 10.1021/acs.bioconjchem.9b00715. View

20.

Xu Y, Huang S, Ma Y, Ding H . Loading of DOX into a tetrahedral DNA nanostructure: the corner does matter. Nanoscale Adv. 2022; 4(3):754-760. PMC: 9416905. DOI: 10.1039/d1na00753j. View