Albumin-hitchhiking self-assembly full-API nanoparticles for imaging-guided photodynamic potentiating tumor...

Disrupting intracellular redox homeostasis may modulate the release of molecular patterns associated with tumor damage, contributing to promoting immunogenic cell death (ICD) for immunotherapy. However, tumors typically exhibit an immunosuppressive microenvironment, which can impede the activation of ICD, thereby enabling immune evasion. In this work, without any excipients and carriers, the full active pharmaceutical ingredient (API) nanoparticles (FeV FANPs) are prepared by the assembly of verteporfin (VER) and iron ions (Fe^III) without any carriers, which possess commendable stability and biocompatibility. Intravenously administered FeV FANPs demonstrate rapid binding to endogenous albumin, facilitating prolonged circulation times in the blood and efficient accumulation within tumor tissues through albumin-assisted targeting mechanisms. Subsequently, FeV FANPs exhibit a GSH-responsive release of VER and Fe^III, resulting in Fe^III-triggered GSH depletion and VER-mediated photodynamic therapy (PDT), which collectively induce intracellular redox imbalances and ferroptosis in tumor cells, thus promoting ICD. FeV FANPs show significant inhibition of both orthotopic and metastatic tumor growth through PDT-amplified immunotherapy, contributing to the advancement of clinically transferable nanoparticles for tumor immunotherapy.