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

Nanoscale
Xingli CunQin He

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...Continue Reading

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Citations

Nov 1, 2018·Journal of Cellular Physiology·Masoud NajafiKeywan Mortezaee
Aug 15, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jin HeXintao Shuai
Jan 1, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jing-Bo MaXiao-Li Zhang
Mar 8, 2020·Colloids and Surfaces. B, Biointerfaces·Maximiliano L AgazziOmar Azzaroni
Mar 11, 2021·Biomaterials·Yuequan WangJin Sun
Aug 29, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Huang YangZhengwei Mao
Aug 19, 2020·ACS Applied Materials & Interfaces·Zipeng ZhangNa Zhang

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Methods Mentioned

BETA
NMR
nanoprecipitation
X-ray
transmission electron microscopy
flow cytometry
xenograft
confocal microscopy
optical microscopy
nuclear magnetic resonance
Fluorescence

Software Mentioned

MATLAB
PHI

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