ORIGINAL RESEARCH article
Front. Chem.
Sec. Nanoscience
This article is part of the Research TopicMicroenvironment-Responsive Organic, Inorganic, and Hybrid Structured Nanoparticles: Synthesis, Therapeutic Strategies, and Imaging ApplicationsView all articles
A Self-Reinforcing Nanoplatform for Triple-Synergistic Therapy: NIR-Triggered Photothermal/Gas/Chemodynamic Therapy of Tumors
Provisionally accepted
- 1Health College of Jiangsu Province, Nan tong, China
- 2Affiliated Hospital of Nantong University, Nantong, China
- 3Nantong University, Nantong, China
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The development of multifunctional nanoplatforms capable of achieving synergistic cancer therapy remains a significant challenge. In this study, we present a CD44-targeted nanocomposite, UiO-SNO@CuS/HA, which integrates photothermal therapy (PTT), nitric oxide (NO) gas therapy, and chemodynamic therapy (CDT) within a single construct. This platform is derived from a UiO-66-SH metal–organic framework (MOF), in which thiol groups are converted into S-nitrosothiols (SNO) for controlled NO release. It is subsequently decorated with ultrasmall CuS nanoparticles (NPs) and coated with hyaluronic acid to facilitate tumor-specific delivery. Under 1064 nm laser irradiation, CuS generates localized photothermal heating, which promotes NO liberation and the release of Cu²⁺ ions. The intracellular reduction of Cu2⁺ to Cu⁺ triggers Fenton-like reactions that yield hydroxyl radicals (•OH) and further stimulate NO generation, establishing a self-perpetuating therapeutic loop. This cascade significantly increases intracellular reactive oxygen species (ROS), disrupts mitochondrial function, and induces apoptosis in HeLa cells, while demonstrating excellent cytocompatibility with normal cells. Collectively, UiO-SNO@CuS/HA represents a rationally designed, feedback-amplified nanosystem that enables potent triple-synergistic tumor therapy.
Keywords: metal-organic framework1, nitric oxide2, chemodynamic therapy3, photothermal therapy4, gas therapy5
Received: 09 Nov 2025; Accepted: 26 Nov 2025.
Copyright: © 2025 Xue, Chen, Chen, Xue, Qian and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Meijuan Qian
Dongzhi Wang
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