Enzyme-Loaded Catalytic Macrophage Vesicles with Cascade Amplification of Tumor-Targeting for Oxygenated Photodynamic Therapy

BACKGROUND: Realizing that the potential of photodynamic therapy (PDT) is hindered by hypoxic microenvironment of tumor section, it is desirable to provide a cascade oxygenation strategy to enhance PDT. METHODS: The hydrophilic catalase protein was covalently linked to the hydrophobic photosensitizer Ce6 to form the nanocomplex Catalase-Ce6 with self-assembly. And the Catalase-Ce6 was loaded in the M1 macrophage vesicles (EVs) with GOX-modified to construct the nanosystem Catalase-Ce6@MEVs. The synergistic effects of PDT induced by Catalase-Ce6@MEVs were evaluated on the subcutaneous MFC tumor model. RESULTS: The construction of Catalase-Ce6 not only solved the insoluble problem of Ce6, but also induced a cascade effects for hydrolyzing glucose and increasing the hydrogen peroxide content, achieving the purpose of oxygenated PDT. Cascade tumor targeting was also realized through the binding between vascular cell adhesion molecule 1 (VCAM-1) of tumor tissue and α4 integrin of EVs and enhanced vascular permeability, triggering by PDT. Besides, in vivo experiments found that the Catalase-Ce6@MEVs presented M2 macrophage polarization effect. CONCLUSION: Catalase-Ce6@MEVs exhibit the cascade targeting ability after laser irradiation and prominent tumor treatment effect in vivo, which may provide new ideas and methods for targeted PDT in clinical practice.