EGFR/MFN2 TARGETED NANOPARTICLES PARTICULARLY USEFUL FOR TREATING MULTIDRUG RESISTANT TRIPLE NEGATIVE BREAST CANCER THROUGH MITOCHONDRIAL INHIBITION

摘要

Application for MDR TNBC significantly increasing the efficacy of TNBC treatment and address a global health concern by blocking the ability of mitochondria to fuse together and with other organelles through a nanomedicine therapy. The development of a dual targeted nanomedicine therapy targeting the epidermal growth factor receptor on the surface of TNBC cancers cells and subcellular targeting of mitochondria through mitofusin 2 (MFN2) targeting (mitofusin mediates inter-mitochondrial fusion and fusion of mitochondria with the endoplasmic reticulum). The combination therapy delivers an MFN2-peptidepolymer construct for blocking MFN2 along with a low dose of BAM? (a BAX activator). Transient blocking of MFN2 reduces cellular energy capacity (through decreased mitochondrial fusion), decrease total protein production (by decreased mitochondrial coupling to the endoplasmic reticulum), increases the susceptibility of the cell to paciitaxel or BAM? (increased efficacy of lower dose), with minimal toxicity to normal cells (as IVIFN2 blocking inhibits mitochondrial fusion not mitochondrial function).