Biodegradable Calcium Phosphate Nanotheranostics with Tumor‐Specific Activatable Cascade Catalytic Reactions‐Augmented Photodynamic Therapy

Abstract Photodynamic therapy (PDT) is exploited as a promising strategy for cancer treatment. However, the hypoxic solid tumor and the lack of tumor‐specific photosensitizer administration hinder the further application of oxygen (O 2 )‐dependent PDT. In this study, a biodegradable and O 2 self‐supplying nanoplatform for tumor microenvironment (TME)‐specific activatable cascade catalytic reactions‐augmented PDT is reported. The nanoplatform (named GMCD) is constructed by coloading catalase (CAT) and sinoporphyrin sodium (DVDMS) in the manganese (Mn)‐doped calcium phosphate mineralized glucose oxidase (GOx) nanoparticles. The GMCD can effectively accumulate in tumor sites to achieve an “off to on” fluorescence transduction and a TME‐activatable magnetic resonance imaging. After internalization into cancer cells, the endogenous hydrogen peroxide (H 2 O 2 ) can be catalyzed to generate O 2 by CAT, which not only promotes GOx catalytic reaction to consume more intratumoral glucose, but also alleviates tumor hypoxia and enhances the production of cytotoxic singlet oxygen from light‐triggered DVDMS. Moreover, the H 2 O 2 generated by GOx‐catalysis can be converted into highly toxic hydroxyl radicals by Mn 2+ ‐mediated Fenton‐like reaction, further amplifying the oxidative damage of cancer cells. As a result, GMCD displays superior therapeutic effects on 4T1‐tumor bearing mice by a long term cascade catalytic reactions augmented PDT.