Functionalized DOPE/TAP Liposomes Bearing Arginine-Rich Peptides for Efficient siRNA Delivery into Triple-Negative Breast Cancer Cells. Biophysical Characterisation of the Complexes

Abstract

Innovative drug delivery platforms are redefining the landscape of modern therapeutics, from dendrimers and liposomes to polymeric systems and metallic nanoparticles. The development of carrier systems that combine safety, biocompatibility and therapeutic efficacy is being focused upon in research. In this study, we designed and functionalised liposomes for the delivery of small interfering RNA (siRNA) that specifically targets and silences EGFR in triple-negative breast cancer (TNBC) cells characterized by EGFR overexpression. DOPE/TAP/R9-based liposomes conjugated with therapeutic siRNA directed against EGFR were investigated to assess their potential as a targeted delivery platform. The study focused on evaluating the biophysical properties of liposome:siEGFR complexes and intracellular trafficking capacity. A suite of analytical techniques, including fluorescence polarisation, circular dichroism, dynamic light scattering, ζ-potential measurements, gel retardation assays and electrophoresis in the presence of nucleases, demonstrated that DOPE/TAP/R9-Chol liposomes form stable and protective complexes with siRNA. Subsequent cellular uptake studies, using flow cytometry and confocal microscopy, confirmed that there was efficient intracellular delivery into the MDA-MB-231 cell line. The results identified an optimal liposome:siRNA formulation and mark a promising step toward the development of a safe and effective siRNA delivery system for biomedical applications.