An oxygen reservoir-irrigated photoimmunotherapy of malignant melanoma

Tumor hypoxia is the pivotal factor limiting the therapeutic efficacy of photodynamic therapy(PDT),and can be partly improved by either the oxygen economizing or the oxygen supplementation strategies.Nevertheless,the current studies scarcely integrated the merits of both strategies and neglected the bottleneck of poor oxygen infiltration in deep tumors,resulting in PDT resistance.Herein,we developed an oxygen reservoir-irrigated PDT which integrates oxygen supply,oxygen economizing,and oxygen infiltration altogether.Specifically,mitochondria-targeted mesoporous prussian blue nanoparticles(Ce6@TPB)were fabricated to bridge the gap between oxygen economizing and oxygen supplementation by reducing oxygen output while increasing oxygen input.Hyaluronidase-loaded microneedles were further developed to pave the way for deep PDT with increased infusion of oxygen and photosensitizer by degrading dense extracellular matrix.The modulation of tumor oxygenation and permeability during PDT leads to the complete eradication of primary melanoma and strong immunogenic cell death.Its further combination with checkpoint-blockade inhibitor greatly suppressed the proliferation of distal tumors by reprogramming immune microenvironments,as evidenced by the depletion of M2 macrophage,increased infiltration of anti-tumor immune cells,and elevated excretion of immune cytokines.Therefore,such an oxygen reservoir-irrigated PDT potentiates powerful photoimmunotherapy and provides a favorable prospect for tumor treatment.