3 years ago

Macroporous silica nanoparticles for delivering Bcl2-function converting peptide to treat multidrug resistant-cancer cells

Macroporous silica nanoparticles for delivering Bcl2-function converting peptide to treat multidrug resistant-cancer cells
Jie Liu, Weixia Xu, Boning Niu, Pengjin Ge, Xiaokun Zhang, Jingjing Xie
The abundance of B cell lymphoma gene 2 (Bcl-2) is closely correlated with the resistance of cancer cells to chemotherapeutic agents, and a peptide derived from orphan nuclear receptor Nur77 can convert Bcl-2 from a protector to a killer of cancer cells. However, successful application of the Bcl-2-converting peptide to treat drug-resistant cancer cells depends on an efficient delivery carrier. Mesoporous silica nanoparticles (MSNs) have been extensively studied as promising candidates for small molecule drug delivery. However, the effective encapsulation and intracellular delivery of peptides using small pore-sized MSNs still remain a great technical challenge. In this paper, an effective delivery platform for Bcl-2-converting peptide was fabricated by us to treat multidrug resistant-cancer cells via tuning the surface functionality of macroporous silica nanoparticles. The resulting large-sized pore silica nanoparticles, especially those modified with thiol group, exhibited the high Bcl-2-converting peptide-loading efficiency of over 40%. Moreover, the peptide induced MCF7/DOX cells into apoptotic status by penetrating cytomembrane into mitochondria and being bound with Bcl-2 to expose the BH3 domain with the aid of various surface functionalities-decorated MSNs. In particular, amine-modified surface of MSNs caused the greater influence on the cell apoptosis-inducing effects of peptide in comparison with other functionalities-modified ones. Taken together, our study, for the first time, demonstrates a special approach towards pore size and surface functionality-collectively modulated silica-based nanostructural material for effective delivery of bio-macromolecules (e.g., Bcl-2-converting peptide) to treat the multidrug resistant-cancer cells with elevated Bcl-2 levels.
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