A size switchable nanoplatform for targeting the tumor microenvironment and deep tumor penetrationElectronic supplementary information (ESI) available. See DOI: 10.1039/c8nr00640g

A size switchable nanoplatform for targeting the tumor microenvironment and deep tumor... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nanoscale Royal Society of Chemistry

A size switchable nanoplatform for targeting the tumor microenvironment and deep tumor penetrationElectronic supplementary information (ESI) available. See DOI: 10.1039/c8nr00640g

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Publisher
The Royal Society of Chemistry
Copyright
This journal is © The Royal Society of Chemistry
ISSN
2040-3364
D.O.I.
10.1039/c8nr00640g
Publisher site
See Article on Publisher Site

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.

Journal

NanoscaleRoyal Society of Chemistry

Published: May 17, 2018

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