Therapeutic co-assemblies for synergistic NSCLC treatment through dual topoisomerase I and tubulin inhibitors.

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State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory & Center for Molecular Imaging and Translational Medicine, School of Public Health, Shenzhen Research Institute of Xiamen University, Xiamen University, Xiamen 361102, China. Electronic address:

Published: January 2025

Camptothecin (CPT) and podophyllotoxin (PPT) function as topoisomerase (TOP) I and tubulin inhibitors, respectively, with potent anticancer effects in a variety of cancers. Despite its promise, the clinical applicability of the combination of CPT and PPT faces challenges, including potential side effect and limited therapeutic efficacy. In this study, we designed co-assembly nanomedicines with the different weight (w/w) ratios of amphiphilic Evans blue conjugated CPT prodrug (EB-ss-CPT) and PPT molecules, denoted as ECT Nano. The co-assembly of EB-ss-CPT and PPT without other excipients has nearly 100% drug loading efficiency and high drug loading content of PPT of up to 74.29 ± 0.90 wt%. Notably, the ECT Nano (1:2) equipped with the ability to inhibit TOP I activity and tubulin polymerization, which provided a highly efficient strategy to improve synergistic efficacy and decrease side toxicity in non-small cell lung cancer mouse model. This work represents a step forward to the development of practical applications for dual TOP I and tubulin inhibitors and especially hopeful to the rational design of combination nanomedicine for therapeutic purposes.

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http://dx.doi.org/10.1016/j.jconrel.2024.11.054DOI Listing

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