2. Academic Validation
  3. Copper peroxide/manganese dioxide nanoparticles crosslinked hyaluronan hydrogel for enhanced chemodynamic/photodynamic/photothermal therapy in breast cancer

Copper peroxide/manganese dioxide nanoparticles crosslinked hyaluronan hydrogel for enhanced chemodynamic/photodynamic/photothermal therapy in breast cancer

  • J Colloid Interface Sci. 2025 Sep 25;703(Pt 1):139121. doi: 10.1016/j.jcis.2025.139121.
Jinlei Wang 1,  Weijun Xu 2,  Junmin Qian 3,  Fei Liang 4,  Yaping Wang 5,  Huichen Zhao 5,  Mofan Xiao 5,  Xinyu Li 5,  Rajiv Kumar Jha 6,  Junyi Wang 6,  Xinyue Liang 6,  Yingbo Wang 7,  Aili Suo 8
Affiliations

Affiliations

  • 1 State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China; School of Clinical Medicine, Xi'an Medical University, Xi'an 710021, China.
  • 2 State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China.
  • 3 State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an 710049, China. Electronic address: jmqian@mail.xjtu.edu.cn.
  • 4 School of Pharmacy, Xi'an Medical University, Xi'an 710021, China.
  • 5 Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
  • 6 School of Clinical Medicine, Xi'an Medical University, Xi'an 710021, China.
  • 7 College of Chemistry and Chemical Engineering, Xinjiang Normal University, Urumqi 830054, China.
  • 8 Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: ailisuo@mail.xjtu.edu.cn.
PMID: 41037888 DOI: 10.1016/j.jcis.2025.139121
Abstract

Therapeutic hydrogels are becoming a promising option of Cancer treatment. However, the simple construction of multifunctional hydrogels under physiological conditions is still a huge challenge. Herein, a chlorin e6 (Ce6)-embedded hyaluronan/CuO2/MnO2 nanocomposite hydrogel (Ce6@HHCM) was developed at physiological pH through an innovative mineralization-induced metal-hydrazide coordinative crosslinking technique. The hydrogel exhibited adjustable degradation rate, outstanding mechanical performance, excellent biosuitability, stimulus-responsive behavior, injectability, and self-healing functionality. Upon intratumoral injection in mouse breast Cancer model, weakly acidic and highly reducible tumor microenvironment triggered the decomposition of CuO2 to Cu+, H2O2 and O2 with the help of catalase-like MnO2, accompanied by both hydrogel breakage and Ce6 release acceleration. The as-generated H2O2 and O2 greatly improved Cu+-based chemodynamic therapy and Ce6-mediated photodynamic therapy, respectively, thus yielding a strong Reactive Oxygen Species (ROS, including •OH and 1O2) storm. Meanwhile, CuO2, MnO2 and disulfide bonds together depleted glutathione to avoid the consumption of ROS. Furthermore, the excellent photothermal heating ability of MnO2 not only directly ablated Cancer cells but also significantly promoted chemodynamic/photodynamic therapy. This study presents a novel mineralization-driven metal-hydrazide coordination crosslinking approach for fabrication of therapeutic hyaluronan hydrogels and provides a four-pronged ROS-elevation strategy to potentiate topical chemodynamic/photodynamic/photothermal triple therapy in breast Cancer.

Keywords

Breast cancer; H(2)O(2)/O(2) self-supplying; Hyaluronan hydrogel; Metal-hydrazide coordination crosslinking; Triple combination therapy.

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