Development of an aptamer capable of multidrug resistance reversal for tumor combination chemotherapy
成果类型：
Article
署名作者：
Wen, Xiaohong; Huang, Zhixiang; Yang, Xiaohai; He, Xiaoxiao; Li, Lie; Chen, Haiyan; Wang, Kemin; Guo, Qiuping; Liu, Jianbo
署名单位：
Hunan University; Hunan University; Hunan University; Hunan University
刊物名称：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN/ISSBN：
0027-14684
DOI：
10.1073/pnas.2321116121
发表日期：
2024-04-09
关键词：
dna aptamers
in-vitro
drug-resistance
cell-selex
cancer
therapeutics
nanocarriers
codelivery
selection
摘要：
Multidrug resistance (MDR) is a major factor in the failure of many forms of tumor chemotherapy. Development of a specific ligand for MDR- reversal would enhance the intracellular accumulation of therapeutic agents and effectively improve the tumor treatments. Here, an aptamer was screened against a doxorubicin (DOX)- resistant human hepatocellular carcinoma cell line (HepG2/DOX) via cell - based systematic evolution of ligands by exponential enrichment. A 50 nt truncated sequence termed d3 was obtained with high affinity and specificity for HepG2/DOX cells. Multidrug resistance protein 1 (MDR1) is determined to be a possible recognition target of the selected aptamer. Aptamer d3 binding was revealed to block the MDR of the tumor cells and increase the accumulation of intracellular anticancer drugs, including DOX, vincristine, and paclitaxel, which led to a boost to the cell killing of the anticancer drugs and lowering their survival of the tumor cells. The aptamer d3- mediated MDR- reversal for effective chemotherapy was further verified in an in vivo animal model, and combination of aptamer d3 with DOX significantly improved the suppression of tumor growth by treating a xenograft HepG2/DOX tumor in vivo. This work demonstrates the feasibility of a therapeutic DNA aptamer as a tumor MDR- reversal agent, and combination of the selected aptamer with chemotherapeutic drugs shows great potential for liver cancer treatments.