Nanoparticle‐Mediated Suicide Gene Therapy for Triple Negative Breast Cancer Treatment

• DOI: 10.1002/adtp.202000007
• Publication Date: 2020-05-11T07:30:02Z
• Authors: Lucia Salvioni; Stefania Zuppone; Francesco Andreata; Matteo Monieri; Serena Mazzucchelli; Caterina Di Carlo; Lucia Morelli; Chiara Cordiglieri; Lorena Donnici; Raffaele De Franc...; Fabio Corsi; Davide Prosperi; Riccardo Vago; Miriam Colombo
• Keywords: Triple-negative breast cancer; Saporin; Suicide gene; Systemic administration

Abstract Systemic chemotherapy has not significantly reduced clinical demand for triple negative breast cancer (TNBC) treatments. To address the need more effective therapy, use of nonviral nanoparticles is explored to deliver suicide gene therapy as valuable alternative protect nucleic acids in bloodstream and improve their tumor uptake. Biocompatible cationic lipid are developed a novel delivery system plasmid encoding saporin. Active targeting accomplished by taking advantage nanoparticle functionalization with U11 peptide, designed be directed toward urokinase plasminogen activator receptor, limiting off‐target toxicity. The antitumor effect U11‐lipid‐protamine‐DNA (U11‐LPD) tested TBNC cells, showing strong prevalence targeted versus nontargeted terms uptake kinetics proliferation inhibition. Transfection green fluorescent protein (GFP) MDA‐MB‐231 cells demonstrated. U11‐LPD administered retro bulbar injection exhibit excellent tropism TNBC orthotopic xenograft mice effectively transfect saporin resulting mass reduction. No systemic toxicity or organ damage discovered after repeated treatments nanoparticles. findings suggest that administration LPD safely allows active inhibition progression even absence specific promoter sequences.