Dual-Metal Organic Framework Nanozyme for Synergistic Photothermal-Chemodynamic Therapy: Copper-Molybdenum Synergism...

To address the dual challenges of chemotherapy toxicity and poor tumor microenvironment regulation in gastric cancer, we developed a copper-molybdenum bimetallic organic framework nanozyme (CMP) that integrates chemodynamic therapy (CDT) and photothermal therapy (PTT). The system leverages synergistic reactive oxygen species (ROS) generation and localized hyperthermia to deliver efficient, low-toxicity treatment.

The CMP nanodrug was synthesized by encapsulating Keggin-type phosphomolybdic acid (H₃PMo_{1 2}O_{4 0}) into copper-based MOF pores via hydrothermal reaction. Physicochemical properties were characterized using transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). Systematic evaluation of antitumor efficacy and biosafety was conducted through in vitro assays (CCK-8, calcein-AM/PI staining, ROS detection) and in vivo xenograft models (subcutaneous implantation of NCI-N87 cells in BALB/c nude mice).

The CMP nanozyme demonstrated exceptional photothermal conversion efficiency (29.4% under 808 nm laser). In vitro experiments revealed significant cytotoxicity with ROS elevation. In vivo studies showed significant tumor growth inhibition without hematotoxicity (WBC, ALT levels showed no statistical significance vs. controls). Histopathology confirmed extensive tumor necrosis with preserved cytoarchitecture in vital organs (heart, liver, spleen, and kidney).

The CMP nanozyme achieves potent antitumor efficacy through photothermal-enhanced Fenton-like reactions, depleting glutathione and amplifying ROS. It suppresses gastric cancer in vivo with minimal systemic toxicity, representing a promising nanoplatform for precision therapy.