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Size and charge dual-transformable mesoporous nanoassemblies for enhanced drug delivery and tumor penetration

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Abstract

A series of biological barriers in a nanoparticle-formulated drug delivery process inevitably result in the current low delivery efficiency, limited tumor penetration and insufficient cellular internalization of drugs. These multiple biological barriers are intimately related to the physicochemical properties of nanoparticles, especially the contradictory demand on size and surface charge for long blood circulation (larger and negative) and deep tumor penetration (smaller) as well as efficient cellular internalization (positive). Herein, we report tumor microenvironment triggered size and charge dual-transformable nanoassemblies. The nanoassembly is realized by immobilizing positive up/downconverting luminescent nanoparticles (U/DCNPs) onto large mesoporous silica nanoparticles (MSNs) via acid-labile bonds to form core@satellite structured MSN@U/DCNPs nanoassemblies, and subsequent capping of charge reversible polymers. At physiological pH, the integrated nanoassemblies with a larger size (∼180 nm) and negative charge can effectively achieve a prolonged blood circulation and high tumor accumulation. While under an acidic tumor microenvironment, the charge reversal of outer polymers and cleavage of linkers between MSNs and U/DCNPs can induce disintegration of the nanoassemblies into isolated MSNs and smaller U/DCNPs, both with a positively charged surface, which thereby potentiate the tumor penetration and cell uptake of dissociated nanoparticles. Combined with the independent near-infrared (NIR)-to-visible and NIR-to-NIR luminescence of U/DCNPs and high surface area of MSNs, the nanoassemblies can implement NIR bioimaging guided chemo- and photodynamic combined therapy with remarkable antitumor efficiency because of the high accumulation and deep tumor penetration induced by the dual transformability of the nanoassemblies.

Graphical abstract: Size and charge dual-transformable mesoporous nanoassemblies for enhanced drug delivery and tumor penetration

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Supplementary files

Article information


Submitted
11 Dec 2019
Accepted
29 Jan 2020
First published
03 Feb 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020, Advance Article
Article type
Edge Article

Size and charge dual-transformable mesoporous nanoassemblies for enhanced drug delivery and tumor penetration

L. Chen, T. Zhao, M. Zhao, W. Wang, C. Sun, L. Liu, Q. Li, F. Zhang, D. Zhao and X. Li, Chem. Sci., 2020, Advance Article , DOI: 10.1039/C9SC06260B

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