Active-oxygenating hollow Prussian blue nanosystems loaded with biomacromolecules for photodynamic/photothermal therapy of cancer and alleviating hypoxic tumors

Such is the hypoxia in solid tumor that Ⅱ-type photodynamic therapy (PDT) has not yet achieved significantly satisfactory consequences. Despite the rapid advancement in nanotechnology-based PDT for alleviating the hypoxic tumor microenvironment, several challenges persist. These include inefficient passive oxygen-supply mechanisms, low stability of oxygen-delivery nanosystems, and the complexity of their modification processes. To address these issues, we developed integrative nanoformulations (HHI NPs) by sequentially inserting biomacromolecule hemoglobin (Hb) and IR783 (photosensitizer) into hollow mesoporous Prussian blue (HPB NPs) through a straightforward and gentle diffusion method. Intriguingly, the resulting hybrid nanocomposites based on hollow mesoporous structure provided stability of biomacromolecule Hb, ensuring active and efficient oxygen delivery. In these nanosystems, HHI NPs equipped with high oxygen-carrying Hb efficiently generated reactive oxygen species over HepG2 cells cultured in hypoxic condition under NIR irradiation. Additionally, HPB NPs served not only as nanocarriers but also as photothermal agents exhibiting excellent photothermal conversion effects. which were beneficial for photothermal therapy (PTT) of cancer. HHI NPs co-loaded with Hb and IR783 not only actively relieved the hypoxic TME through the stable protection of the hollow structure from HPB NPs, but also achieve the significant synergistic therapy by combining PDT and PTT for tumor treatment.