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Issue 21, 2018
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A size switchable nanoplatform for targeting the tumor microenvironment and deep tumor penetration

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Abstract

The complex tumor microenvironment (TME) in solid tumors forms physiological barriers to the efficient delivery of nanomedicine, leading to limited therapeutic efficacy. Herein, to overcome these physiological barriers and improve the therapeutic effect, we constructed a novel size-adjustable nanoplatform for efficient drug delivery into solid tumors. The smart size-switchable nanoplatform (DGL/DOX@PP) was prepared by conjugating small dendrigraft poly-L-lysine (DGL) to poly(ethylene glycol)–poly(caprolactone) micelles via a matrix metalloproteinase 2 (MMP-2)-sensitive peptide. DGL/DOX@PP had an initial size of 100 nm and a nearly neutral charge, rendering the system able to take advantage of the enhanced permeability and retention effect. After extravasation from the tumor vessels, small DGL/DOX nanoparticles (∼30 nm) were rapidly released from DGL/DOX@PP in response to MMP-2 in the TME. This process of particle size alteration greatly enhanced the nanoparticle penetration into both multicellular spheroids (MCSs) and solid tumors. In vivo results demonstrated that compared with small and non-switchable nanoparticles, particles from the size-switchable nanoplatform achieved excellent antitumor efficacy in 4T1 tumor-bearing mice. This size-adjustable nanoplatform provides a multifunctional strategy for TME modulation and tumor penetration.

Graphical abstract: A size switchable nanoplatform for targeting the tumor microenvironment and deep tumor penetration

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Publication details

The article was received on 23 Jan 2018, accepted on 20 Apr 2018 and first published on 17 May 2018


Article type: Paper
DOI: 10.1039/C8NR00640G
Citation: Nanoscale, 2018,10, 9935-9948
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    A size switchable nanoplatform for targeting the tumor microenvironment and deep tumor penetration

    X. Cun, M. Li, S. Wang, Y. Wang, J. Wang, Z. Lu, R. Yang, X. Tang, Z. Zhang and Q. He, Nanoscale, 2018, 10, 9935
    DOI: 10.1039/C8NR00640G

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