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Nanoparticle‐Mediated Suicide Gene Therapy for Triple Negative Breast Cancer Treatment
Author(s) -
Salvioni Lucia,
Zuppone Stefania,
Andreata Francesco,
Monieri Matteo,
Mazzucchelli Serena,
Di Carlo Caterina,
Morelli Lucia,
Cordiglieri Chiara,
Donnici Lorena,
De Francesco Raffaele,
Corsi Fabio,
Prosperi Davide,
Vago Riccardo,
Colombo Miriam
Publication year - 2020
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202000007
Subject(s) - triple negative breast cancer , saporin , transfection , genetic enhancement , cancer research , suicide gene , systemic administration , chemistry , gene delivery , medicine , breast cancer , pharmacology , cancer , biology , cytotoxicity , in vivo , in vitro , gene , biochemistry , immunotoxin , microbiology and biotechnology
Systemic chemotherapy has not significantly reduced clinical demand for triple negative breast cancer (TNBC) treatments. To address the need for more effective therapy, the use of nonviral nanoparticles is explored to deliver suicide gene therapy as valuable alternative to protect nucleic acids in the bloodstream and improve their tumor uptake. Biocompatible cationic lipid nanoparticles are developed as a novel delivery system of a suicide plasmid gene encoding saporin. Active targeting is accomplished by taking advantage of nanoparticle functionalization with U11 peptide, designed to be directed toward urokinase plasminogen activator receptor, limiting off‐target toxicity. The antitumor effect of U11‐lipid‐protamine‐DNA (U11‐LPD) nanoparticles are tested in TBNC cells, showing a strong prevalence of targeted versus nontargeted nanoparticles in terms of uptake kinetics and proliferation inhibition. Transfection of green fluorescent protein (GFP) plasmid in MDA‐MB‐231 cells is demonstrated. U11‐LPD nanoparticles administered by retro bulbar injection exhibit excellent tumor tropism in TNBC orthotopic xenograft mice and effectively transfect TNBC cells with saporin plasmid resulting in tumor mass reduction. No systemic toxicity or organ damage is discovered after repeated treatments with nanoparticles. The findings suggest that systemic administration of targeted LPD nanoparticles to deliver saporin safely allows for active inhibition of cancer progression even in the absence of specific promoter gene sequences.