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Bioinspired Diselenide-Bridged Mesoporous Silica Nanoparticles For Dual-Responsive Protein Delivery.

D. Shao, Mingqiang Li, Z. Wang, X. Zheng, Yeh-Hsing Lao, Zhimin Chang, F. Zhang, M. Lu, J. Yue, Hanze Hu, Huize Yan, L. Chen, W. Dong, K. Leong
Published 2018 · Materials Science, Medicine

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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.
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