Tumor Microenvironment-Response Calcium Phosphate Hybrid Nanoparticles Enhanced siRNAs Targeting Tumors In Vivo

: Short interfering RNA (siRNA)-based therapy has a high potential for application in cancer gene therapy. However, delivery of siRNA to target cells is limited by many factors such as serum ribonuclease (RNase) degradation, off-target effects, and inadequate cellular uptake. In this study, an enzyme-response PEG/Lipids/calcium phosphate hybrid delivery system was constructed for siRNA. The nearly neutral charged siRNA@NP2 was resistant to serum-induced degradation. Compared with the non-enzyme-response siRNA@NP1, siRNA@NP2 had efficient delivery in both SMMC-7721 cell lines and SMMC-7721-bearing nude mice. Moreover, safety evaluation of the nanoparticles revealed that they had no significant toxicity both in vitro and in vivo. The developed siRNA@NP2 delivery system presents an efficient tool for siRNA-based cancer gene therapy in vivo.