Comparative Study\nof Functionalized Carbosilane Dendrimers\nfor siRNA Delivery: Synthesis, Cytotoxicity, and Biophysical Properties

Efficient and safe carriers of genetic material are crucial\nfor\nadvancing gene therapy. Three new series of cationic dendritic nanocarriers\nbased on a carbosilane scaffold, differentiated by peripheral modifications:\nsaccharide (CS-glyco), amine (CS-N),\nand phosphonium dendrimers (CS-P) were designed for binding, protecting,\nand releasing polyanionic compounds like therapeutic siRNA. Besides\nintroducing synthetic methodology, this study brings a unique direct\ninterstructural comparison of 16 dendritic nanovector’s characteristics,\naddressing a gap in typical research that focuses on uniform structural\ntypes. The study evaluates the dendrimer’s <i>in vitro</i> cytotoxicity, biophysical properties, and complexation capabilities\nin comparison with widely used PAMAM dendrimers. CS-glyco and PAMAMs\nwere significantly less toxic to MCF-7 and THP-1 cell lines than were\nCS-N and CS-P, despite having the same peripheral charge density.\nNotably, CS-glyco maintained biocompatibility comparable to analogous\nneutral CS glycodendrimers, underscoring the exceptional capability\nof sugar coating to reduce toxicity. Dendriplexes formed from these\nnanocarriers protected siRNA from RNase degradation and facilitated\nits release in the presence of heparin, highlighting its potential\nin gene delivery applications. The study provides a background for\nfuture in-depth investigations into the introduced dendritic nanocarriers,\nwhich show significant potential for advancing drug delivery.