Redox-triggered hyaluronic acid polymersomes for co-delivery of methotrexate and curcumin to breast cancer cells.

Among nanoparticles, polymersomes have drawn notable interest due to their ability to simultaneously load two drugs, their suitable size, high stability, and controlled drug release. In this study, an amphiphilic, redox-sensitive hyaluronic acid-polycaprolactone block copolymer was synthesized for targeted drug delivery to CD44-overexpressing breast cancer MDA-MB-231 cells. Nanopolymersomes were formed via nanoprecipitation and co-loaded with curcumin and methotrexate. The particle sizes, with and without the drugs, were examined using DLS and reported as 182.53 ± 6.08 nm and 217.45 ± 6.23 nm, respectively. The structure of the particles was confirmed by FE-SEM and TEM. In the in vitro release study, the polymersomes showed enhanced drug release under high-glutathione conditions (66 % CUR, 47 % MTX) compared to low-glutathione conditions (43 % CUR, 28 % MTX). The dual-drug-loaded nanopolymersomes demonstrated superior anticancer efficacy at a lowest drug concentration ratio. The cellular uptake showed significantly higher uptake of drug-loaded polymersomes compared to free drugs over a 4-h period. Flow cytometry analysis further revealed that the dual-drug-loaded polymersomes induced apoptosis in more than 72.9 % of the cells. The results demonstrated that redox-sensitive hyaluronic acid-based polymersomes effectively target CD44 receptors and enable intracellular co-delivery of anticancer drugs, resulting in significantly reduced viability of breast cancer cells.