Polyphosphazenes for RNA delivery in brain cancer immunotherapy

Abstract

RNA-based therapies are increasingly recognized in cancer immunotherapy, especially for targeting poorly immunogenic brain tumors such as glioblastoma. RNA molecules can modulate immune responses by selectively activating or silencing specific genes, thereby mitigating tumor-induced immunosuppression. However, clinical translation remains challenging due to RNA's limited pharmacokinetic properties. To address this, we propose utilizing polyelectrolyte complexes, PECs, composed of polyorganophosphazenes, PPZs, highly versatile, synthetic, and biodegradable polymers, for RNA delivery. This thesis examines PPZ-based PECs for delivering siRNA and mRNA sequences to various tumor-associated cell populations, with the goal of enhancing immunotherapeutic strategies for brain tumor cancer.