Prussian Blue modified Metal Organic Frameworks for imaging guided synergetic tumor therapy with hypoxia modulation

Abstract In this study, a hybrid material UIO-66-NH2/PB were synthesized through the modification of Prussian Blue on the surface of Metal Organic Frameworks for synergetic tumor therapy with hypoxia modulation. It was found that UIO-66-NH2/PB has good photo-thermal performance and photo-thermal stability, suitable for photo-thermal treatment. Dissolved oxygen analysis showed that UIO-66-NH2/PB can catalyze H2O2 into O2. It was proved that this process is accompanied by the generation of ·OH. Furthermore, with the irradiation of 808 nm for 5min, the TMB solution becomes darker blue, proving that more free radicals are produced. The produced O2 can be used to modulate the hypoxia of tumor to improve the anti-cancer efficiency, and the generated ·OH can kill cancer cells to achieve chemo-dynamic therapy. Doxorubicin (DOX) was selected as a model drug and the DOX loading of UIO-66-NH2/PB was 67%. Drug release experiments showed that DOX was not nearly released in pH 7.4, while 78% DOX was released in pH5.8 after 40 h, demonstrating the excellent pH-responsive release. In addition, with the irradiation of 808 nm for 5min, 87% DOX was released in pH 5.8, indicating photo-thermal effect could help achieve better release effect. The different cytotoxicity to L-02 cells and HeLa cells of UIO-66-NH2/PB shows UIO-66-NH2/PB is only harmful to cancer cells, indicating that Fenton-like reaction only occurred in tumor to generate ·OH. In vivo experiment showed synergetic therapy can achieve satisfactory treatment efficiency. Therefore, UIO-66-NH2/PB is expected to combine multiple treatments to improve anti-cancer effect.