Targeting nano-regulator based on metal–organic frameworks for enhanced immunotherapy of bone metastatic prostate cancer

Abstract Bone metastasis is the main cause of death in patients with prostate cancer (PCa), but there lacks effective treatment method. Immunotherapy shows new hopes for bone metastatic PCa patients, while efficacy still unsatisfactory and limited by unique immunosuppressive microenvironment site. Here, we developed a bone-targeted nano-delivery system as nano-regulator to enhance immunotherapy PCa. The nanosystem was assembled via coordination between phytic acid (PA) Fe 3+ form nano-sized metal–organic framework (MOF), through which mitoxantrone (MTO) encapsulated. At cellular level, showed selective cytotoxicity towards RM-1 cells over immune cells, could induce tumor immunogenic cell (ICD) improve immunogenicity tumor. Moreover, able ubiquitination TGFβ receptor (TβR) on promote its degradation, thus serving block functions TGF-β, an abundant cytokine that has systematically effect microenvironment. Upon intravenous injection, nanoparticle pro-longed blood circulation targeting accumulation into site, imposed robust anti-tumor combination αCTLA-4. In addition, destruction significantly alleviated after reduce skeletal-related events. Overall, this work provides biocompatible nanomedicine restore sensitivity enhanced blocking TGF-β signaling pathway.