Polyphenol-mediated biomimetic MOFs hybrid nanoplatform for catalytic cascades-enhanced cancer targeted combination therapy

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Recently, the development of multifunctional nanoplatforms for synergistic therapy is highly attractive in cancer treatment. Herein, a cancer cell membrane-coated biomimetic nanoplatform (termed as mPAGT) was designed through a simple and versatile polyphenol-mediated coating strategy for a catalytic cascades-enhanced tumor targeted combination therapy. Porphyrin MOFs (PCN) were selected as a nano-photosensitizer and then an endogenous nitric oxide (NO) donor l-arginine (l-Arg) was loaded into the framework to obtain PA nanoplatforms; Subsequently, glucose oxidase (GOx) was coated on the surface through the interactions between protein and polyphenol and the purified murine breast cancer cell membrane was further decorated to form the resulting nanoplatforms mPAGT NPs. The prepared nanoplatforms exhibited an excellent drug loading capability (9.59% for l-Arg and 33.75% for GOx) and homologous targeting ability. Meanwhile, the mPAGT NPs could initiated a cascade reaction included GOx catalyzed oxidation of glucose, nano-photosensitizer based 1O2-producing, and ROS-mediated the release of NO, and induce an obvious apoptosis with the highest apoptotic ratio of 86.2%. Moreover, the in vivo experimental results further confirmed that our multifunctional nanoplatforms possessed negligible systemic toxicity and promising potential for the treatment of tumor through the catalytic cascades-enhanced synergistic therapy.