Synergistically enhanced multienzyme catalytic nanoconjugates for efficient cancer therapy

Abstract

Tumors are complex and highly variable, making it difficult for a single treatment strategy to be significantly effective for cancer therapy. Herein, we report a robust cascade biomimetic nanoplatform that integrates chemiluminescence-induced photodynamic therapy (CL-PDT), Fenton reaction-based chemodynamic therapy (CDT), and glucose oxidase (GOD)-mediated starvation therapy to synergistically enhance cancer treatment. For the nanoplatform of CPPO@porphyrin-MOF@Cancer cell membrane-GOD (C₁@M@C₂G), the ferric ion-linked porphyrin-MOF can trigger a Fenton reaction to reach CDT, the carried CPPO as an energy donor is used to excite a photo-sensitive porphyrin-MOF in situ to generate singlet oxygen (¹O₂) for PDT, GOD catalyzes glucose into H₂O₂ and gluconic acid to realize starvation therapy, and the cancer cell membrane wrapped onto the nanoparticle plays a key role in homologous targeting, which is conducive to achieving better therapeutic effects. Significantly, the porphyrin-MOF with catalase-like activity can generate O₂ to effectively relieve tumor hypoxia, thereby enhancing the catalytic effect of GOD and the efficacy of PDT. Additionally, the produced H₂O₂ and gluconic acid can further improve the CPPO-H₂O₂-triggered CL-PDT and promote the low pH-dependence Fenton reaction-based CDT, respectively. Both in vitro and in vivo studies showed that the constructed nanoplatform displays an excellent cooperative anti-tumor performance, so we firmly believe that this simple nanoplatform broadens the pathway to fight against cancer through effective cascade catalysis.