The MCM/Lys-Cys nanodevices for the efficient gene delivery: An approach towardsMCP1gene manipulation using CRISPR technology

Abstract

Breast cancer continues to be the most common malignancy among women worldwide, requiring novel therapeutic approaches. This research investigates an innovative gene delivery strategy employing mesoporous silica nanoparticles (MCM-41) modified with lysine and cysteine (Lys-Cys) for the effective delivery of CRISPR-Cas9 plasmids aimed at the monocyte chemoattractant protein-1 (MCP-1/CCL2) gene. Bioinformatics analysis of the TCGA-BRCA dataset revealed substantial deregulation of CCL2 in breast cancer, underscoring its involvement in tumor growth and inflammation. The MCM/Lys-Cys nanocarrier demonstrated remarkable biocompatibility and effectively encapsulated a plasmid containing GFP, promoting superior cellular uptake in MDA-MB-231 breast cancer cells compared to conventional techniques. Functional experiments demonstrated that CRISPR/Cas9-mediated suppression of CCL2 markedly decreased cell proliferation, migration, and invasion, highlighting the promise of this targeted gene therapy strategy in breast cancer management. The findings indicate that the MCM/Lys-Cys nanosystem presents a viable non-viral approach for precise gene editing, potentially boosting therapeutic efforts against breast cancer by modulating inflammatory pathways.