Suicide-Gene Transfection of Tumor-tropic Placental Stem Cells employing Ultrasound-Responsive Nanoparticles

TL;DR

This study develops ultrasound-responsive silica nanoparticles for transfecting tumor-tropic mesenchymal stem cells with suicide genes, enabling targeted cancer therapy through a Trojan-horse approach.

Contribution

It introduces a novel non-viral nanovector system for gene transfection in mesenchymal stem cells using ultrasound-responsive nanoparticles.

Findings

Successful transfection of stem cells with GFP and suicide genes

Conversion of pro-drug into toxic compound demonstrated in co-cultured cancer cells

Effective gene delivery using ultrasound-responsive nanovectors

Abstract

A Trojan-horse strategy for cancer therapy employing tumor-tropic mesenchymal stem cells transfected with a non-viral nanovector is here presented. In this sense, ultrasound-responsive mesoporous silica nanoparticles were coated with a polycation (using two different molecular weights), providing them with gene transfection capabilities that were evaluated using two different plasmids. First, the expression of Green Fluorescent Protein was analyzed in Decidua-derived Mesenchymal Stem Cells after incubation with the silica nanoparticles. The most successful nanoparticle was then employed to induce the expression of two suicide genes: cytosine deaminase and uracil phosphoribosyl transferase, which allow the cells to convert a non-toxic pro-drug (5-fluorocytosine) into a toxic drug (5-Fluorouridine monophosphate). The effect of the production of the toxic final product was also evaluated in a cancer cell line (NMU cells) co-cultured with the transfected vehicle cells, Decidua-derived Mesenchymal Stem Cells.