Tumor Microenvironment Adaptable Nanoplatform for O2 Self-Sufficient Chemo/Photodynamic Combination Therapy

Malignant proliferation of tumor cells induces abnormal tissue microenvironments, leading to therapeutic resistance and poor therapeutic outcome. In this paper, manganese dioxide (MnO₂) nanoshells are coated on a porphyrinic metal–organic framework of porous coordination network (PCN)-224 for doxorubicin (DOX) loading and hyaluronic acid (HA) modification to obtain an intelligent nanoplatform of PCN@MnO₂@DOX@HA (PMDH). Benefiting from the HA functionalization, PMDH prefers to accumulate in tumor sites and enhance the cellular uptake by CD44-overexpressed tumor cells. Subsequently, the internalized PMDH could catalyze the abundant H₂O₂ in cells into O₂ to relieve tumor hypoxia. Further, the MnO₂ nanoshells of PMDH could be degraded into Mn²⁺ for magnetic resonance imaging with glutathione reduction and the release of DOX. By integrating the O₂ self-sufficiency with glutathione reduction abilities, PMDH possesses highly potent chemo/photodynamic combination therapeutic effects against hypoxic tumors. Significantly, PMDH exhibits a good biocompatibility with a low cardiotoxicity and negligible systemic side effects, which provides a new insight in developing tumor microenvironment adaptable nanoplatforms for synergistic tumor theranostics.