Fine‐Tuned Polymer Nanoassembly for Codelivery of Chemotherapeutic Drug and siRNA

Abstract

AbstractSuccessful clinical application of siRNA to liver‐associated diseases reinvigorates the RNAi therapeutics and delivery vectors, especially for anticancer combination therapy. Fine tuning of copolymer‐based assembly configuration is highly important for a desirable synergistic cancer cell‐killing effect via the codelivery 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 is synthesized. Three distinct assemblies (i.e., nanosized micelle, nanosized polymersome, and microparticle) are acquired, along with the increase in PDPA block length. Furthermore, the as‐obtained polymersome can efficiently codeliver 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 is synergistically killed by the DOX‐ and siArf6‐coloading polymersome (namely PLD@DOX/siArf6). PLD@DOX/siArf6 may serve as a robust nanomedicine for anticancer therapy.