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

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Chen, Liang
Zhao, Tiancong
Zhao, Mengyao
Wang, Wenxing
Sun, Caixia
Liu, Lu
Li, Qin
Zhang, Fan
Zhao, Dongyuan
Li, Xiaomin
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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.

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Chemical Science

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© The Author(s) 2020. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0) License, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.

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Chen, L; Zhao, T; Zhao, M; Wang, W; Sun, C; Liu, L; Li, Q; Zhang, F; Zhao, D; Li, X, Size and charge dual-transformable mesoporous nanoassemblies for enhanced drug delivery and tumor penetration, Chemical Science, 2020, 11 (10), pp. 2819-2827