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A pH-responsive dissociable mesoporous silica-based nanoplatform enabling efficient dual-drug co-delivery and rapid clearance for cancer therapy

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Abstract

The balance between tumor accumulation and renal clearance has severely limited the efficacy of mesoporous silica-based drug nanocarriers in cancer therapy. Herein, a pH-responsive dissociable mesoporous silica-based nanoplatform with efficient dual-drug co-delivery, tumor accumulation and rapid clearance for cancer therapy is achieved by adjusting the wetting of the mesoporous silica surface. At pH 7.4, the synthesized spiropyran- and fluorinated silane-modified ultrasmall mesoporous silica nanoparticles (SP-FS-USMSN) self-assemble to form larger nanoclusters (denoted as SP-FS-USMSN cluster) via hydrophobic interactions, which can effectively co-deliver anticancer drugs, doxorubicin hydrochloride (Dox) and curcumin (Cur), based on the mesopores within SP-FS-USMSN and the voids among the stacked SP-FS-USMSN. At pH 4.5–5.5, the conformational conversion of spiropyran from a “closed” state to an “open” state causes the wetting of the SP-FS-USMSN surface, leading to the dissociation of the SP-FS-USMSN cluster for drug release and renal clearance. The in vitro and in vivo studies demonstrate that the Cur and Dox co-loaded SP-FS-USMSN cluster (Cur-Dox/SP-FS-USMSN cluster) possesses great combined cytotoxicity, and can accumulate into tumor tissue by its large size-favored EPR effect and potently suppress tumor growth in HepG2-xenografted mice. This research demonstrates that the SP-FS-USMSN cluster may be a promising drug delivery system for cancer therapy and lays the foundation for practical mesoporous silica-based nanomedicine designs in the future.

Graphical abstract: A pH-responsive dissociable mesoporous silica-based nanoplatform enabling efficient dual-drug co-delivery and rapid clearance for cancer therapy

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Supplementary files

Article information


Submitted
09 Feb 2020
Accepted
24 Apr 2020
First published
30 Apr 2020

Biomater. Sci., 2020, Advance Article
Article type
Paper

A pH-responsive dissociable mesoporous silica-based nanoplatform enabling efficient dual-drug co-delivery and rapid clearance for cancer therapy

Y. He, L. Shao, I. Usman, Y. Hu, A. Pan, S. Liang and H. Xu, Biomater. Sci., 2020, Advance Article , DOI: 10.1039/D0BM00204F

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