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

TLDR

Controlled delivery of protein therapeutics remains a challenge. The study reports the design of biodegradable mesoporous silica nanoparticles incorporating diselenide bonds for oxidative and redox dual‑responsive protein delivery. The nanoparticles encapsulate RNase A electrostatically in 8‑10 nm pores and release it upon oxidative or redox‑induced degradation, while cancer‑cell membrane cloaking provides homologous targeting and immune‑invasion properties. In vitro and in vivo studies show that the cell‑membrane‑coated, dual‑responsive degradable MSNs enhance circulation time, tumor accumulation, and anti‑cancer efficacy with low toxicity, indicating promise for protein and nucleic acid delivery.

Abstract

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.