Synergizing Pt-O-Mo Coupling and Electron Gradient: A Nanozyme Paradigm for Low-Dose Tumor Radiosensitization

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapy

Background:

• Nanozymes exhibit limited catalytic activity and electron transfer, hindering radiotherapy efficacy against hypoxic tumors.
• Tumor microenvironment (TME) hypoxia causes radioresistance and limits reactive oxygen species (ROS) generation, reducing treatment effectiveness.
• Current nanozyme radiosensitizers often require high radiotherapy doses or combination drugs for modest outcomes.

Purpose of the Study:

• To develop a novel nanozyme with enhanced catalytic activity and electron transfer for improved radiotherapy.
• To address nanozyme limitations in hypoxic TME and overcome tumor radioresistance.
• To create a Pt-anchored MoO_x (MPP) nanozyme with a gradient electron-transfer interface.

Main Methods:

• Synthesized Pt-anchored MoO_x (MPP) nanozyme using a surface defect-ligand reduction strategy.
• Characterized MPP nanozyme for Pt loading, Pt-O-Mo interactions, oxygen vacancies, and interfacial electron pool.
• Utilized Density Functional Theory (DFT) calculations to confirm interface effects on electron transfer and H₂O₂ dissociation.
• Evaluated MPP nanozyme's catalase-like activity, turnover number, and electron transfer efficiency.
• Assessed MPP's performance in a hypoxic TME, including its cascade reactions and synergy with low-dose radiotherapy in vivo.

Main Results:

• MPP nanozyme achieved high Pt loading (34.39 ± 0.92 wt%) with a gradient electron-transfer interface.
• DFT calculations confirmed accelerated electron transfer and reduced H₂O₂ dissociation barrier.
• MPP exhibited superior catalase-like activity (3884.53 U mg^-1) and electron transfer efficiency (1.75).
• In acidic TME, MPP orchestrated a cascade reaction to relieve hypoxia and generate ROS (•O₂^-/¹O₂).
• MPP amplified low-dose (6 Gy) radiotherapy efficacy, achieving 75.24% tumor inhibition with no systemic toxicity.

Conclusions:

• The gradient electron-transfer interface strategy in MPP nanozymes significantly enhances catalytic activity and electron transfer.
• MPP effectively combats TME hypoxia and radioresistance, amplifying radiotherapy efficacy.
• This approach offers a promising paradigm for high-efficacy, low-toxicity, tumor-specific cancer therapy.