Engineering Aptamers with Selectively Enhanced Biostability in the Tumor Microenvironment

被引：25

作者：

Xie, Sitao ^{[1
,2
]}

Wang, Zhimin ^{[2
]}

Fu, Ting ^{[1
,2
]}

Zheng, Liyan ^{[2
]}

Wu, Hui ^{[2
]}

He, Lei ^{[1
,2
]}

Huang, Huidong ^{[1
,2
]}

Yang, Cai ^{[1
,2
]}

Wang, Ruowen ^{[3
]}

Qian, Xu ^{[1
]}

Qiu, Liping ^{[2
]}

Tan, Weihong ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Sci, Zhejiang Canc Hosp, Inst Basic Med & Canc IBMC, Canc Hosp,Univ Chinese Acad Sci, Hangzhou 310022, Zhejiang, Peoples R China

[2] Hunan Univ, State Key Lab Chemo Biosensing & Chemometr, Coll Chem & Chem Engn, Coll Biol,Aptamer Engn Ctr Hunan Prov,Mol Sci & B, Changsha 410082, Hunan, Peoples R China

[3] Shanghai Jiao Tong Univ, Inst Mol Med IMM, Coll Chem & Chem Engn, Renji Hosp,Sch Med, Shanghai 200127, Peoples R China

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2022年 / 61卷 / 31期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

Aptamers; Biostability; Molecular Engineering; Nucleic Acids; Tumor Microenvironment; ANTISENSE OLIGONUCLEOTIDES; MOLECULAR RECOGNITION; DNA APTAMER; STABILITY; LIGANDS; PROBES;

D O I：

10.1002/anie.202201220

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Aptamers are emerging as promising molecular tools in cancer-targeted theranostics. Improving their in vivo stability has been a critical issue in promoting clinical translation, but such efforts could lead to more serious side effects resulting from prolonged retention in healthy organs. To address this problem, we developed an environment-responsive stabilization strategy for the selective enhancement of aptamer biostability in the tumor microenvironment (TME). Briefly, by means of the end extension of an ATP-responsive protection (ARP) module, the designed aptamer could be protected from nuclease degradation through the specific incorporation of ATP. Based on our in vivo results, this ARP-aptamer probe was effectively accumulated in tumors via aptamer-based molecular recognition. It showed selectively prolonged tumor retention time, but rapid digestion in healthy organs. Our strategy should provide a new paradigm for the development of organ-specific nucleic acid-based imaging and therapeutic agents.

引用

页数：5

共 36 条

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