Various nanocarriers for photosensitizers have been developed to solve the problems of limiting the clinical utility of photodynamic therapy (PDT); however, to date, no carriers capable of supplying oxygen have been reported. We reported the development of a novel system composed of red blood cell (RBC)-derived vesicles (RDVs) generated by osmotic stress and demonstrated the capacity of RDVs for encapsulating and delivering external cargo into targeted cells due to the cellular uptake of RDVs. In this study, protoporphyrin IX (PpIX)-encapsulated RDVs (PpIX@RDVs) were prepared by the hypotonic incorporation of PpIX into RDVs in an aqueous environment, characterized, and utilized for PDT of cancer. PpIX@RDVs were rapidly uptaken by tumor cells via endocytosis in vitro, and the highly phototoxic effect of PpIX@RDVs was demonstrated upon irradiation. Superoxide anion (O(2) ) and singlet oxygen ((1)O(2)) were involved in PpIX@RDV-induced cell apoptosis and necrosis. Finally, we demonstrated that RDVs with an oxygen supply capacity have potential as versatile delivery vehicles for efficient PDT.
