Ablation of Gap Junction Protein Improves the Efficiency of Nanozyme‐Mediated Catalytic/Starvation/Mild‐Temperature Photothermal Therapy

Abstract

Reactive oxygen species (ROS)‐mediated tumor catalytic therapy is typically hindered by gap junction proteins that form cell‐to‐cell channels to remove cytotoxic ROS, thereby protecting tumor cells from oxidative damage. In this work, a multifunctional nanozyme, FePGOGA, is designed and prepared by Fe(III)‐mediated oxidative polymerization (FeP), followed by glucose oxidase (GOx) and GAP19 peptides co‐loading through electrostatic and π–π interactions. The FePGOGA nanozyme exhibits excellent cascade peroxidase‐ and glutathione‐oxidase‐like activities that efficiently catalyze hydrogen peroxide conversion to hydroxyl radicals and convert reduced glutathione to oxidized glutathione disulfide. The loaded GOx starves the tumors and aggravates tumor oxidative stress through glucose decomposition, while GAP19 peptides block the hemichannels by inducing degradation of Cx43, thus increasing the accumulation of intracellular ROS, and decreasing the transport of intracellular glucose. Furthermore, the ROS reacts with primary amines of heat shock proteins to destroy their structure and function, enabling tumor photothermal therapy at the widely sought‐after mild temperature (mildPTT, ≤45 °C). In vivo experiments demonstrate the significant antitumor effectof FePGOGA on cal27 xenograft tumors under near‐infrared light irradiation. This study demonstrates the successful ablation of gap junction proteins to overcome resistance to ROS‐mediated therapy, providing a regulator to suppress tumor self‐preservation during tumor starvation, catalytic therapy, and mildPTT.

Recent Advancements in the Formulation of Nanomaterials-Based Nanozymes, Their Catalytic Activity, and Biomedical Applications

“…The elimination of tumor cells via ROS-assisted therapy by FePGOGA, a multifunctional nanozyme, is designed by oxidative polymerization of iron, glucose oxidase, and GAP19 peptide. 130 The fabrication of SAzyme by encapsulation of camptothecin and Pd-C based on agarose hydrogel system promotes the immunogenic killing of cancer cells and ameliorates anticancer potential. 131 Furthermore, pyrite nanozyme exhibits dual enzymatic-like activity of peroxidase and glutathione oxidase which facilitates apoptosis in tumor cells by generating numerous hydroxyl radicals and depleting reduced glutathione levels.…”

“…Simultaneously, the consumption of glucose would suppress the proliferation of cancer cells. The elimination of tumor cells via ROS-assisted therapy by FePGOGA, a multifunctional nanozyme, is designed by oxidative polymerization of iron, glucose oxidase, and GAP19 peptide . The fabrication of SAzyme by encapsulation of camptothecin and Pd-C based on agarose hydrogel system promotes the immunogenic killing of cancer cells and ameliorates anticancer potential .…”

Prussian blue nanozymes: progress, challenges, and opportunities

“…In recent years, significant progress has been made in nanozyme research due to the rapid advancements in nanotechnology, biotechnology, catalysis science, and computational science. 101 This progress includes the expansion of nanozyme types, 102 modulation of catalytic activity, 103,104 elucidation of catalytic mechanisms, 105 and broadening applications. 106 Initially, nanozyme research focused on mimicking superoxide dismutase using nanozyme fullerene derivatives, which then expanded to include iron oxide nanoparticles mimicking peroxidase, and eventually led to the development of the ROS-scavenging nanozyme PBNZ.…”

Albumin-Based Cyanine Crizotinib Conjugate Nanoparticles for NIR-II Imaging-Guided Synergistic Chemophototherapy

“…The long wavelength emission, which occurs when the absorbed photon energy is relaxed through the radiation channel, offers a possible use for fluorescence imaging (FLI), which has the benefits of high sensibility, real-time trackability, high spatiotemporal resolution, and noninvasiveness. In particular, FLI in the second near-infrared region (NIR-II, 1000–1700 nm) enables us to penetrate deep into the tissue with minimal tissue interference and photodamage. − On the other hand, photodynamic therapy (PDT) and photothermal therapy (PTT) can be applied simultaneously as cancer treatment strategies by utilizing photoinduced reactive oxygen species (ROS) generation and thermogenesis. − …”