Issue 24, 2021

Tandem molecular self-assembly for selective lung cancer therapy with an increase in efficiency by two orders of magnitude

Abstract

In situ self-assembly of prodrug molecules into nanomedicine can elevate the therapeutic efficacy of anticancer medications by enhancing the targeting and enrichment of anticancer drugs at tumor sites. However, the disassembly and biodegradation of nanomedicine after enrichment prevents the further improvement of the efficiency, and avoiding such disassembly and biodegradation remains a challenge. Herein, we rationally designed a tandem molecular self-assembling prodrug that could selectively improve the therapeutic efficacy of HCPT against lung cancer by two orders of magnitude. The tandem molecular self-assembly utilized an elevated level of alkaline phosphatase and reductase in lung cancer cells. The prodrug first self-assembled into nanofibers by alkaline phosphatase catalysis and was internalized more efficiently by lung cancer cells than free HCPT. The resulting nanofiber was next catalyzed by intracellular reductase to form a more hydrophobic nanofiber that prevented the disassembly and biodegradation, which further significantly improved the efficacy of HCPT against lung cancer both in vitro and in vivo.

Graphical abstract: Tandem molecular self-assembly for selective lung cancer therapy with an increase in efficiency by two orders of magnitude

Supplementary files

Article information

Article type
Paper
Submitted
22 fev 2021
Accepted
19 may 2021
First published
24 may 2021

Nanoscale, 2021,13, 10891-10897

Tandem molecular self-assembly for selective lung cancer therapy with an increase in efficiency by two orders of magnitude

D. Zheng, J. Liu, Y. Ding, L. Xie, Y. Zhang, Y. Chen, R. Peng, M. Cai, L. Wang, H. Wang, J. Gao and Z. Yang, Nanoscale, 2021, 13, 10891 DOI: 10.1039/D1NR01174J

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