TNBC (Triple Negative Breast Cancer Specific) Ligand-displaying Exosomes Using RNA Nanotechnology for Targeted Cytosol Delivery of RNAi without Endosome Entrapment

Recently, Drs. Daniel Binzel and Dan Shu proved that exosomes can be utilized as carriers to deliver siRNA to TNBC cancer cells and inhibit cancer growth. Preliminary data has shown the mechanism behind the high efficiency of gene silencing to be the cytosolic delivery of siRNA via exosomes without endosomal entrapment. In this study, we will investigate the targeting and delivery mechanism of siRNA to TNBC cells via exosomes that display TNBC binding ligands for targeted delivery with a goal of selecting a lead TNBC therapeutic candidate for potential clinical translation. The goal of this project is to accomplish the following three objectives: 1) specific targeting of TNBC cells; 2) escaping endosomal entrapment and achieving efficient cytosolic delivery; and 3) avoiding nonspecific accumulation in healthy vital organs to avoid unwanted toxicity and side effects. My laboratory has established several TNBC PDX models, I will collaborate with Drs. Binzel and Shu to evaluating anti-tumor efficacy (tumor regression, gene knockdown, and survival curve) of TNBC ligand-displaying exosomes in PDX models.