Fine-Tuned Polymer Nanoassembly for Codelivery of Chemotherapeutic Drug and siRNA
Successful 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.
危险品化学品经营许可证（带存储）