UVA-responsive Fe₃O₄@ZnO nanocarrier grafted with anti-EGFR antibody for precision delivery of Nrf2-siRNA and brusatol: A novel platform for integrated photodynamic, gene, and chemotherapy

  • Int J Biol Macromol. 2025 Feb 17;305(Pt 2):141153. doi: 10.1016/j.ijbiomac.2025.141153.
Qian Ren  1 ,  Tingting Tian  2 ,  Bin Wang  3 ,  Jun Pan  4 ,  Yong Huang  5 ,  Li Zhong  6 ,  Yehong Wang  2 ,  Xia Wang  2 ,  Xiao Huang  7
Affiliations
  • 1. Hunan Provincial Key Laboratory of Dong Medicine, Biomedical Research Institute, Hunan University of Medicine, Huaihua 418000, PR China; Key Laboratory for Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
  • 2. Hunan Provincial Key Laboratory of Dong Medicine, Biomedical Research Institute, Hunan University of Medicine, Huaihua 418000, PR China.
  • 3. Obesity and Metabolic Diseases Research Center, Department of Physiology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: [email protected].
  • 4. Key Laboratory for Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China. Electronic address: [email protected].
  • 5. College of Lab Medicine, Hebei North University, Key Laboratory of Biomedical Materials of Zhangjiakou, Zhangjiakou 075000, PR China.
  • 6. Key Laboratory for Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, PR China.
  • 7. Hunan Provincial Key Laboratory of Dong Medicine, Biomedical Research Institute, Hunan University of Medicine, Huaihua 418000, PR China. Electronic address: [email protected].
PMID: 39971059 DOI: 10.1016/j.ijbiomac.2025.141153
Abstract

Photodynamic therapy (PDT) remains underutilized as a primary Cancer treatment due to the limited lethality of Reactive Oxygen Species (ROS) and poor targeting efficiency of traditional photosensitizers. This the aim of the study is to develop a Fe₃O₄@ZnO nanoparticle Photosensitizer co-loaded with anti-EGFR antibody, brusatol, and Nrf2-siRNA to improve the therapeutic effect of PDT. This system can be guided to tumors by a magnetic field and further targets Cancer cells through EGFR-specific binding. Under UVA light, brusatol and Nrf2-siRNA are released, enabling combined chemo-, gene, and photodynamic therapy. With the Photosensitizer treatment, ROS levels in cutaneous squamous cell carcinoma cells were elevated by 191.09 ± 10.02 % through suppression of Nrf2 and its associated antioxidant defenses, significantly enhancing cell lethality and reducing cell viability by 80.43 ± 9.37 %. In vivo studies further demonstrated a tumor suppression rate of 76.30 ± 5.12 % in nude mice, highlighting the robust anti-tumor efficacy of the Photosensitizer and its potential for clinical application in targeted Cancer therapy. The biocompatibility and high therapeutic efficacy of this Photosensitizer highlight its promise as a safer and more effective option for treating cutaneous squamous cell carcinoma.

Keywords
Combined therapy; Cutaneous squamous cell carcinoma; Precise targeting; Reactive oxygen species lethality; Zinc oxide.
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