A “self-accelerating endosomal escape” siRNA delivery nanosystem for significantly suppressing hyperplasia via blocking the ERK2 pathway

and ERK2-siRNA, our designed TRCs-Aco revealed more excellent biocompatibility including hemocompatibility and cytocompatibility. Unexpectedly, TRCs-Aco exhibited stronger ERK2 silencing efficiency at the level of mRNA and protein, which was mainly due to its remarkable self-accelerating endosomal escape. Definitive evidence demonstrated that this ternary ERK2-siRNA delivery system significantly prevented the migration of VSMCs and decreased the dermal thickness in bleomycin-treated mice. In brief, this unique structured system could provide a valuable nanoplatform for highly efficient siRNA delivery in VSMCs, and it might hold great potential in guiding ERK2-siRNA-based proliferative disease therapy.