Photomechanical engineering of immunogenic whole-cell vaccines by laser-induced vapor nanobubbles for bladder cancer prophylaxis
Whole-cell cancer vaccines can provide broad tumor-antigen repertoires, but their efficacy depends on manufacturing methods that inactivate tumor cells while preserving immunogenic danger signals. Here we show that laser-induced vapor nanobubbles (VNB) generated from dextran-coated iron oxide nanoparticles provide a drug-free photomechanical route to engineer immunogenic whole-cell vaccines against bladder cancer. Using MB49 murine urothelial carcinoma cells, we established VNB conditions that induced rapid tumor-cell killing together with calreticulin exposure and extracellular ATP and HMGB1 release. Rapid cell killing and calreticulin exposure were also reproduced in the molecularly distinct UPPL1541 bladder cancer model, supporting the generalizability of the early photomechanical response across bladder cancer cell lines. Vaccination with VNB-killed MB49 cells reduced tumor incidence and growth after subcutaneous challenge and enhanced splenocyte-mediated antitumor activity against MB49 cells. In an orthotopic bladder cancer model, vaccination prevented MRI-detectable tumor formation and was associated with marked early bladder enrichment of CD8 T cells and inflammatory monocytes. A single administration of the VNB-generated vaccine preparation showed no evident local or systemic toxicity during seven days of follow-up. These findings provide proof of concept for an externally triggered, drug-free manufacturing approach in which short laser irradiation induces rapid photomechanical killing of tumor cells on demand, generating immunogenic whole-tumor-cell vaccine preparations for further evaluation in therapeutic, post-resection and tumor-derived settings.