PtMo‐Au Metalloenzymes Regulated Tumor Microenvironment for Enhanced Sonodynamic/Chemodynamic/Starvation Synergistic Therapy

Abstract

The clinical application of sonodynamic therapy (SDT) is greatly limited by the low quantum yield of sonosensitizers and tumor microenvironment (TME). Herein, PtMo‐Au metalloenzyme sonosensitizer is synthesized by modulating energy band structure of PtMo with Au nanoparticles. The surface deposition of Au simultaneously solves the carrier recombination and facilitates the separation of electrons (e−) and holes (h+), effectively improving the reactive oxygen species (ROS) quantum yield under ultrasound (US). The catalase‐like activity of PtMo‐Au metalloenzymes alleviates hypoxia TME, thus enhancing the SDT‐induced ROS generation. More importantly, tumor overexpressed glutathione (GSH) can serve as the hole scavenger, which is accompanied by a persistent depletion of the GSH, thus inactivating GPX4 for the accumulation of lipid peroxides. The distinctly facilitated SDT‐induced ROS production is coupled with chemodynamic therapy (CDT)‐induced hydroxyl radicals (•OH) to exacerbate ferroptosis. Furthermore, Au with glucose oxidase mimic activity can not only inhibit intracellular adenosine triphosphate (ATP) production and induce tumor cell starvation but also generate H2O2 to facilitate CDT. In general, this PtMo‐Au metalloenzyme sonosensitizer optimizes the defects of conventional sonosensitizers through surface deposition of Au to regulate TME, providing a novel perspective for US‐based tumor multimodal therapy.

A copper-loaded self-assembled nanoparticle for disturbing the tumor redox balance and triple anti-tumor therapy

“…10,11 Similarly, SDT-mediated toxicity is based on the generation of reactive oxygen (ROS) via ultrasound (another exogenous trigger), oxygen and sonosensitizers. 12,13 Additionally, CDT, as a novel-emerging strategy, is a ROS-mediated therapy which catalyzes hydrogen peroxide (H 2 O 2 ) to generate highly reactive hydroxyl radicals ( OH) through a Fenton or Fenton-like reaction. [14][15][16] Nevertheless, the complicated tumor microenvironment (TME) poses great challenges for current cancer therapy strategies.…”

Cascade Self-Generation of Carbon Monoxide Triggered by Photoinduced Holes for Efficient Hypoxic Tumors Therapy

“…To attain this, several H 2 O 2 -generation agents (β-lapachone, − glucose oxidase, , and vitamin C, or its imitations, etc. ), metal peroxides (calcium peroxide, , magnesium peroxide, zinc peroxide, copper peroxide, or combined metal peroxides), metalloenzyme , have been designed and utilized to supply H 2 O 2 in situ and GSH depletion in cancer cells. For example, dendritic mesoporous organosilicon nanoparticles modified with glucose oxidase have been employed to supply H 2 O 2 for chemodynamic therapy (CDT).…”

A Multifunctional Covalent Organic Framework Nanozyme for Promoting Ferroptotic Radiotherapy against Esophageal Cancer

“…Due to advantages, such as easy synthesis and high catalytic activity, conferred by nanozymes, they have come to be considered as a next generation of enzyme mimics. , Nanozymes have very recently been successfully applied to ferroptosis-based tumor therapy. − Among the various nanozymes reported in the literature, covalent organic framework (COF) nanozymes have already exhibited excellent potential in sensing, − antibiosis, − and antitumor treatment − owing to their high crystallinity, intrinsic porosity, structural regularity, design flexibility, customizable pore environment, versatility, and exceptional stability. , Although they have not yet been used for radiotherapy sensitization, COF-based nanozymes should, in principle, be synthesizable via function-oriented material design. If synthesized, the multifunctional COF nanozymes so obtained would not only increase X-ray energy deposition (owing to the introduction of high- Z elements) but also exert multiple nanozyme effects, inducing sustained lipid peroxidation and reductant depletion, thereby disrupting cellular redox homeostasis and enhancing radiosensitivity …”