Computable structured aptamer for targeted treatment of ovarian cancer

Luoshan Ruan; Liting Han; Xin Li; Xin Chen; Gege Sun; Xinyu Wang; Yan Luo; Chuanqi Gu; Xiaolong Shi

doi:10.3389/fgene.2023.1170260

Computable structured aptamer for targeted treatment of ovarian cancer

Front Genet. 2023 May 3:14:1170260. doi: 10.3389/fgene.2023.1170260. eCollection 2023.

Authors

Luoshan Ruan¹, Liting Han¹, Xin Li¹, Xin Chen², Gege Sun¹, Xinyu Wang¹, Yan Luo¹, Chuanqi Gu¹, Xiaolong Shi²

Affiliations

¹ Department 2 of Gynecology, Remin Hospital of Wuhan University, Wuhan, China.
² Institute of Computing Science and Technology, Guangzhou University, Guangzhou, China.

Abstract

Nucleolin protein expression is higher on the ovarian cancer cell surface. AS1411, a DNA aptamer, can bind with nucleolin protein specifically. In this study, we developed HA and ST DNA tiles to assemble six AS1411 aptamers to deliver doxorubicin. In addition, to superior serum stability and drug loading, HA-6AS and ST-6AS outperformed TDN-AS in cellular uptake. HA-6AS and ST-6AS exhibited satisfactory targeted cytotoxicity and achieved resounding lysosomal escape. Moreover, when injected into nude mice subcutaneous xenograft models, HA-6AS reached the peak in tumor more quickly than ST-6AS, and better expressed the active targeting ability of AS1411. Our study suggests that designing appropriate DNA tiles to assemble different aptamers to deliver different chemotherapeutic drugs is a promising treatment for ovarian cancer.

Keywords: AS1411 aptamer; DNA tile; doxorubicin; nucleolin; ovarian cancer.

Grants and funding

This study was supported by the National Natural Science Fund of China (Grant No. 62172302).