SBIR CONCEPT AWARD "THERAPEUTICS" - TARGETED DELIVERY OF FERROPTOSIS INDUCERS FOR TREATMENT OF ADRENOCORTICAL CARCINOMA

This proposal seeks to develop a novel therapeutic approach for recurrent or metastatic adrenocortical carcinoma (ACC), a rare and aggressive malignancy of the adrenal cortex. The current five-year survival rate for metastatic ACC is less than 15%. The proposed work will establish feasibility of a scavenger receptor class B type 1 (SCARB1) targeted nanoparticle encapsulating a ferroptosis-inducing agent. SCARB1, an integral membrane protein found in many cell types, is best known for its role in selective uptake of cholesteryl esters from high-density lipoproteins. Ferroptosis, an iron-dependent, non-apoptotic mode of regulated cell death, has produced intriguing therapeutic responses in tumor models, exploiting tumor-related metabolic reprogramming to selectively kill tumor cells. ACC cells are highly susceptible to ferroptosis and exhibit elevated surface expression of SCARB1. Therefore, exploration of a dual-selective formulation is warranted. Activities will be divided into three sequential aims: (1) optimizing nanoparticle encapsulation of ferroptosis-inducing agents, (2) evaluating ferroptotic potential in relevant cell lines, and (3) demonstrating tumor effect in a murine model of ACC. This project seeks to produce a formulation suitable for further development and IND-enabling studies. This novel and scientifically supported strategy could transform treatment for ACC and other tumors.