Augmented cellular trafficking and endosomal escape of porous silicon nanoparticles via zwitterionic bilayer polymer surface engineering

摘要: The development of a stable vehicle with low toxicity, high cellular internalization, efficient endosomal escape, and optimal drug release profile is key bottleneck in nanomedicine. To overcome all these problems, we have developed successful layer-by-layer method to covalently conjugate polyethyleneimine (PEI) poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface undecylenic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming bilayer zwitterionic nanocomposite containing free positive charge groups hyper-branched PEI disguised by PMVE-MA polymer. smoothness, hydrophilicity NPs considerably improved colloidal plasma stabilities via enhanced suspensibility repulsion. Furthermore, despite negative polymer-conjugated NPs, trafficking escape were significantly increased both MDA-MB-231 MCF-7 breast cancer cells. Remarkably, also showed that conjugation amine highly toxic UnTHCPSi-PEI (Un-P) carboxylic renders acceptable safety features system preserves properties proton sponge mechanism available located inside layer. Moreover, double layer protection not only controlled aggregation reduced but sustained an anticancer drug, methotrexate, further cytotoxicity drug-loaded particles. These results provide proof-of-concept evidence such polymer-based PSi nanocomposites can be extensively used as promising candidate for cytosolic delivery.