Bioinspired Diselenide-Bridged Mesoporous Silica Nanoparticles for Dual-Responsive Protein Delivery

Controlled delivery of protein therapeutics remains a challenge. Here, the inclusion of diselenide-bond-containing organosilica moieties into the framework of silica to fabricate biodegradable mesoporous silica nanoparticles (MSNs) with oxidative and redox dual-responsiveness is reported. These diselenide-bridged MSNs can encapsulate cytotoxic RNase A into the 8-10 nm internal pores via electrostatic interaction and release the payload via a matrix-degradation controlled mechanism upon exposure to oxidative or redox conditions. After surface cloaking with cancer-cell-derived membrane fragments, these bioinspired RNase A-loaded MSNs exhibit homologous targeting and immune-invasion characteristics inherited from the source cancer cells. The efficient in vitro and in vivo anti-cancer performance, which includes increased blood circulation time and enhanced tumor accumulation along with low toxicity, suggests that these cell-membrane-coated, dual-responsive degradable MSNs represent a promising platform for the delivery of bio-macromolecules such as protein and nucleic acid therapeutics.