Biocompatible nanoparticles sensing the matrix metallo-proteinase 2 for the on-demand release of anticancer drugs in 3D tumor spheroids

Colloids and Surfaces. B, Biointerfaces
Marco CantisaniPaolo A Netti

Abstract

The balance between dose-dependent tolerability, effectiveness and toxicity of systemically administered antitumor drugs is extremely delicate. This issue highlights the striking need for targeted release of chemotherapeutic drugs within tumors. In this work, a smart strategy of drug targeting to tumors relying upon biodegradable/biocompatible nanoparticles releasing cytotoxic drugs after sensing physiological variations intrinsic to the very nature of tumor tissues is exploited. Here, the well-known over-expression of matrix metallo-proteinase 2 (MMP2) enzyme in tumors has been chosen as a trigger for the release of a cytotoxic drug. Nanoparticles made up of a biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) - block - polyethylene glycol (PEG) copolymer (namely PELGA), blended with a tumor-activated prodrug (TAP) composed of a MMP2-sensitive peptide bound to doxorubicin (Dox) and to PLGA chain have been produced. The obtained devices are able to release Dox specifically upon MMP2 cleavage of the TAP. More interestingly, they can sense the differences in the expression levels of endogenous MMP2 protein, thus modulating drug penetration within a three-dimensional (3D) tumor spheroid matrix, accordingly. Therefore, the prop...Continue Reading

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Citations

Oct 7, 2016·Colloids and Surfaces. B, Biointerfaces·Valentina BelliPaolo A Netti
Jan 27, 2017·Bioconjugate Chemistry·Dirk van den BrandWouter P R Verdurmen
Aug 15, 2017·Journal of Drug Targeting·Juan LiRongmei Wang
Jul 11, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Andrea P FalangaDaniela Guarnieri
Apr 11, 2021·Advanced Drug Delivery Reviews·Sabina PozziRonit Satchi-Fainaro

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