Engineering Aptamers with Selectively Enhanced Biostability in the Tumor Microenvironment

Sitao Xie; Zhimin Wang; Ting Fu; Liyan Zheng; Hui Wu; Lei He; Huidong Huang; Cai Yang; Ruowen Wang; Xu Qian; Liping Qiu; Weihong Tan

doi:10.1002/anie.202201220

Engineering Aptamers with Selectively Enhanced Biostability in the Tumor Microenvironment

Angew Chem Int Ed Engl. 2022 Aug 1;61(31):e202201220. doi: 10.1002/anie.202201220. Epub 2022 Jun 21.

Authors

Sitao Xie^{1

2}, Zhimin Wang², Ting Fu^{1

2}, Liyan Zheng², Hui Wu², Lei He^{1

2}, Huidong Huang^{1

2}, Cai Yang^{1

2}, Ruowen Wang³, Xu Qian¹, Liping Qiu², Weihong Tan^{1

2

3}

Affiliations

¹ The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
² Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.
³ Institute of Molecular Medicine (IMM), Renji Hospital, School of Medicine, College of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China.

PMID: 35536294
DOI: 10.1002/anie.202201220

Abstract

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.

Keywords: Aptamers; Biostability; Molecular Engineering; Nucleic Acids; Tumor Microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate
Aptamers, Nucleotide*
Humans
Neoplasms* / drug therapy
Nucleic Acids*
Tumor Microenvironment

Substances

Aptamers, Nucleotide
Nucleic Acids
Adenosine Triphosphate