Biomimetic Degradable Dendritic Mesoporous Silica Nanoparticles Co-delivery SN38/siRNA For Breast Cancer Therapy

Biomacromolecule therapeutics is intrinsically susceptible to degradation and denaturation.Nanoformulations are promising delivery vehicles for therapeutic biomacromolecules(antibody,gene and so on).However,their applications in these areas still face many challenges including in vivo stability,premature leakage and accurate tumor recognition.In this study,a new generally applicable strategy for tumor-targeted delivery of biomacromolecules was developed through the hierarchical integration of degradable large-pore dendritic mesoporous silica nanoparticles(d MSNs)and cyclodextrin-modified polyamidoamine(PAMAM-CD)dendrimers.The orifice rim of the d MSN was modified with ROS-responsive nitrophenyl-benzyl-carbonate(NBC)groups while disulfide-bonded azido ligands were subsequently grafted onto the inner channel walls via heterogeneous functionalization.The PAMAM-CD was then interred into the dendritic pores via click reactions and supramolecularly loaded with archetypal hydrophobic small-molecule anticancer model drug(SN-38)and therapeutic model gene(Bcl-2 siRNA),after which d MSN was eventually coated with 4T1 cancer cell membrane(CCM).Experimental evidence demonstrated that the synthesized nanocarrier could efficiently deliver the therapeutic cargos to target cancer cells and release them in the tumor cytosol in the cascade-responsive manner.This biomimetic nanoplatform presents a novel strategy to efficiently deliver biomolecular therapeutics in a tumor-targeted manner.