Cleavable Cationic Carbosilane Dendrimers with pH-Tunable Charge as siRNA Carriers.

Gene therapy is a cutting-edge technique for the prevention or treatment of diseases, which demands the development of biocompatible and efficient vectors. Additionally, for cancer therapy, a precise control on the vectors' response at different pH values is required due to the heterogeneity of the tumors' pH. Many nonviral vectors are based on quaternary ammonium compounds, thus exhibiting potential toxicity and persistence. In this work, we designed a new family of cationic carbosilane dendrimers, which exhibits two differential features: a pH-tunable charge, which can modulate the interaction between the nanocarrier and the siRNA, and a cleavable core, which can further enhance the release of the cargo. We thoroughly explored the structural and biophysical characteristics of the new dendrimers at different pH values: 4.5, 5.5, and 7.4. Additionally, biocompatibility in tumoral and nontumoral cells was evaluated along with the hemolytic effect. Finally, we provided a proof-of-concept for their use as pH-responsive nanocarriers of siRNA.