Gliomas are highly aggressive brain tumors and complete tumor resection is not achievable as residual tumor cells routinely infiltrate the surrounding functional brain tissue and are protected by the blood brain barrier (BBB). The BBB presents a significant obstacle for effective delivery of therapeutic agents to the central nervous system. The BBB forms a highly selective semipermeable border that prevents solutes in the circulating blood from crossing into the intracranial environment. Thus, there is an urgent need for new approaches for drug delivery through the BBB to gliomas. To address these major unmet medical needs, here we propose to develop new nanoparticles for delivering STING agonist to gliomas. We will develop nanoparticles that can be tuned with different targeting moieties and effectively delivered to gliomas; elicit anti-tumor immune response by converting the “cold” glioma tumors to “hot” tumors; eradicate established gliomas; and generate sustained anti-gliomas immunity. This Supplement application focuses on applying the knowledge gained from the parent R01 grant to target STING agonists to gliomas and achieve anti-tumor immunity against gliomas. Therefore, this represents a new and complementary research component that directly relates to original goals of the grant and broadens its translational potential and application.