Multifunctional Hollow MnO2@Porphyrin@Bromelain Nanoplatform for Enhanced Photodynamic Therapy

Abstract Photodynamic therapy (PDT) has been showing great potential in cancer treatment. However, the efficacy of PDT is always limited by the intrinsic hypoxic tumor microenvironment (TME) and the low accumulation efficiency of photosensitizers in tumors. To address the issue, a multifunctional hollow multilayer nanoplatform (H‐MnO 2 @TPyP@Bro) comprising manganese dioxide, porphyrin (TPyP) and bromelain (Bro), is developed for enhanced photodynamic therapy. MnO 2 catalyzes the intracellular hydrogen peroxide (H 2 O 2 ) to produce oxygen (O 2 ), reversing the hypoxic TME in vivo. The generated O 2 is converted into singlet oxygen ( 1 O 2 ) by the TPyP shell under near‐infrared light, which can inhibit tumor proliferation. Meanwhile, the Bro can digest collagen in the extracellular matrix around the tumor, and can promote the accumulation of H‐MnO 2 @TPyP@Bro in the deeper tumor tissue, further improving the therapeutic effect of PDT. In addition, MnO 2 can react with the overexpressed glutathione in TME to release Mn 2+ . Consequently, Mn 2+ not only induces chemo‐dynamic therapy based on Fenton reaction by converting H 2 O 2 into hydroxyl radicals, but also activates the Mn 2+ ‐based magnetic resonance imaging. Therefore, the developed H‐MnO 2 @TPyP@Bro nanoplatform can effectively modulate the unfavorable TME and overcome the limitations of conventional PDT for cancer diagnostic and therapeutic.