LAUSR

Natural enzyme-based catalytic cascades hold great promise for cancer therapy, but their clinical utility is greatly hindered by the loss of their functions during in vivo delivery. Herein, we report a plasmonic tri-enzyme integrated metal-organic framework (plasEnMOF) nanoplatform with high-efficiency enzyme cascades for synergistic starvation, thermodynamic and plasmonic hyperthermia tri-modal therapy of hypoxic tumors. This plasEnMOFs are created with encapsulation of near-infrared II (NIR-II) plasmonic Au nanorods and natural enzymes - catalase (CAT), glucose oxidase (GOx) and horseradish peroxidase (HRP) within zeolitic imidazolate framework-8 (ZIF-8) MOFs. As a tri-enzyme cascade system, the plasEnMOFs effectively deplete intratumoral glucose and generate toxic reactive oxygen species (ROS) for starvation therapy and chemodynamic therapy (CDT) combined with the plasmonic hyperthermia therapy (PHT). We also demonstrate the enhanced glucose consumption and ROS generation by the NIR-II plasmonic photothermal effect. The improved chemo- and thermo-tolerance of the encapsulated natural enzymes within the protective ZIF-8 MOFs is evidenced. With the integrated enzyme cascades and NIR-II photothermal effects, our plasEnMOFs are demonstrated with exceptional therapeutic effects on 4T1 xenograft tumors through the combined starvation/CDT/PHT therapy. This work highlights the superiority of natural enzyme cascade systems integrated in plasmonic MOFs for high-efficiency enzymatic cancer therapy. This article is protected by copyright. All rights reserved.