2. Academic Validation
  3. A multifunctional oxidative stress amplifier for synergistic disruption of redox homeostasis and enhanced cancer therapy

A multifunctional oxidative stress amplifier for synergistic disruption of redox homeostasis and enhanced cancer therapy

  • J Colloid Interface Sci. 2025 Aug 28;702(Pt 1):138870. doi: 10.1016/j.jcis.2025.138870.
Jie Lv 1,  Shuangling Wang 2,  Haozhe Zhang 3,  Yanhua Zhong 1,  Xinjian Guo 1,  Wei Guo 4,  Meng Li 5
Affiliations

Affiliations

  • 1 College of Pharmacy, Key Laboratory of Innovative Drug Development and Evaluation, Hebei Medical University, Shijiazhuang, 050017, China; National Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei Medical University, Shijiazhuang 050017, China.
  • 2 College of Pharmacy, Key Laboratory of Innovative Drug Development and Evaluation, Hebei Medical University, Shijiazhuang, 050017, China; Department of Environmental and Chemical engineering, Hebei Vocational University of Industry and technology, Shijiazhuang 050091, China.
  • 3 College of Pharmacy, Key Laboratory of Innovative Drug Development and Evaluation, Hebei Medical University, Shijiazhuang, 050017, China.
  • 4 College of Pharmacy, Key Laboratory of Innovative Drug Development and Evaluation, Hebei Medical University, Shijiazhuang, 050017, China; National Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: weiguo@hebmu.edu.cn.
  • 5 College of Pharmacy, Key Laboratory of Innovative Drug Development and Evaluation, Hebei Medical University, Shijiazhuang, 050017, China; National Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei Medical University, Shijiazhuang 050017, China. Electronic address: limeng@hebmu.edu.cn.
PMID: 40902490 DOI: 10.1016/j.jcis.2025.138870
Abstract

Emerging nanomedicines that target and disrupt redox homeostasis present a compelling yet technically demanding strategy for Cancer therapy. Herein, a multifunctional oxidative stress amplifier, denoted as C-COF@MnO2-BSA-FA/Ce6 (CMBFC), was engineered to disrupt redox homeostasis through synergistic mechanisms precisely. The nanoplatform was constructed with a core of N-doped carbon nanospheres derived from covalent organic frameworks (C-COF), which was then coated by an in situ mineralized MnO2 layer. This structured nanoplatform was further loaded with the Photosensitizer chlorin e6 (Ce6) and functionalized with bovine serum albumin-folic acid (BSA-FA) for folate receptor targeting. Surface engineering improved biocompatibility and stability in vivo and facilitated passive accumulation at tumor sites. Within the tumor microenvironment, the MnO2 shell responded to elevated glutathione (GSH) levels and acidic conditions, degrading to release Mn2+ and oxygen (O2). This process alleviated tumor hypoxia to augment the Ce6-exerted photodynamic therapy (PDT). The exposed C-COF, exhibiting peroxidase-like activity, boosted the Fenton-like reaction of Mn2+, thereby enhancing the chemodynamic therapy (CDT) effect. Meanwhile, the nanoplatform exhibited excellent GSH-depleting capability to avoid the potential Reactive Oxygen Species (ROS) consumption, thus triply amplifying tumor oxidative stress. Based on the synergistic effect of multiple oxidative damages and photothermal ablation, the nanoplatform showed boosted antitumor efficacy in both cellular and animal models. This work offers novel perspectives on advancing precise and highly effective therapy in Cancer treatment.

Keywords

Chemodynamic therapy; Glutathione oxidase-like activity; N-doped carbon nanospheres; Redox homeostasis; TME responsive.

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