Fine-Tuned Polymer Nanoassembly for Co-Delivery of Chemotherapeutic Drug and siRNA.

Successful clinical application of siRNA to liver-associated diseases reinvigorates the RNAi therapeutics and delivery vectors, especially for anti-cancer combination therapy. Fine tuning of copolymer-based assembly configuration was highly important for a desirable synergistic cancer cell-killing effect via the co-delivery of chemotherapeutic drug and siRNA. Herein, an amphiphilic triblock copolymer methoxyl poly(ethylene glycol)-block-poly(L-lysine)-block-poly(2-(diisopropyl amino)ethyl methacrylate) (abbreviated as mPEG-PLys-PDPA or PLD) consisting of a hydrophilic diblock mPEG-PLys and a hydrophobic block PDPA was synthesized. Three distinct assemblies (i.e., nano-sized micelle, nano-sized polymersome, and microparticle) were acquired, along with the increase in PDPA block length. Furthermore, the as-obtained polymersome could efficiently co-deliver doxorubicin hydrochloride (DOX) as a hydrophilic chemotherapeutic model and siRNA against ADP-ribosylation factor 6 (siArf6) as an siRNA model into cancer cell via lysosomal pH-triggered payload release. PC-3 prostate cell was synergistically killed by the DOX- and siArf6-coloading polymersome (namely PLD@DOX/siArf6). PLD@DOX/siArf6 may serve as a robust nanomedicine for anti-cancer therapy. This article is protected by copyright. All rights reserved.