Abstract
The regulation of immunosuppressive microenvironments in tumors through targeted drug delivery shows promise for immunochemotherapy in bladder cancer. Drawing inspiration from stealth tactics, a nano-vehicle camouflaged with platelets (PLTs) was developed to enable precise delivery and trigger pyroptosis for tumor immunotherapy. Methods: Erdafitinib (Erda) was nano-sized and encapsulated in PLTs to construct nano-Erda@PLT. Characterization of the PLTs camouflaged nano-vehicle was conducted using Zetasizer, SEM, and confocal laser scanning microscopy. The excellent targeted delivery property of the PLTs nano-vehicle was investigated through intravital imaging, three-dimensional microspheres, and SEM. Validation of pyroptosis in bladder cancer cells via the caspase-3/GSDME pathway was performed using western blot, immunofluorescence, and ELISA tests. Immunotherapy by nano-Erda@PLT treatment in vivo was confirmed using H&E, immunohistochemical, and flow cytometry. Lastly, the side effects of nano-Erda@PLT were assessed. Results: Proteomic analysis revealed that the activation of p-selectin on platelets facilitated the identification of nano-Erda@PLT targeted therapies. Nanoscale of Erda released in response to adenosine diphosphate, facilitated intratumoral permeation. This could contribute to an upregulation of the key proteins of pyroptosis, caspase-3 and GSDME, in bladder cancer cells due to nano-Erda@PLT accumulation. Additionally, the burst release of numerous inflammatory factors may enhance the system's adaptive immune response. In a bladder cancer animal model, this treatment was found to regulate the immunosuppressive microenvironment, resulting in effective tumor immunotherapy and the induction of a long-lasting, robust immune memory. Conclusion: PLTs-camouflaged nano-vehicles enable nano-Erda-mediated tumor immunotherapy through the induction of pyroptosis. These findings introduce a novel approach in exploring nanomaterial-mediated pyroptosis for cancer immunotherapy.