Ginger-Derived Exosome-Like Nanoparticles Loaded With Indocyanine Green Enhances Phototherapy Efficacy for Breast Cancer

  • Int J Nanomedicine. 2025 Jan 30:20:1147-1169. doi: 10.2147/IJN.S478435.
Zhaoming Guo  #  1  2 ,  Guqing Li  #  2 ,  Lanjun Shen  2 ,  Jiawei Pan  2 ,  Danni Dou  2 ,  Yuwei Gong  2 ,  Wanwan Shi  2 ,  Yuhua Sun  2 ,  Yi Zhang  2 ,  Kun Ma  2 ,  Changhao Cui  2 ,  Wenxin Li  3  4 ,  Qiang Liu  5 ,  Xudong Zhu  1  4  6
Affiliations
  • 1. Department of General Surgery, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, 110042, People's Republic of China.
  • 2. School of Chemical Engineering, Marine and Life Sciences, Dalian University of Technology, Panjin, Liaoning, 124221, People's Republic of China.
  • 3. The second Department of Hepatopancreatobiliary Surgery, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, 110042, People's Republic of China.
  • 4. Liaoning Provincial Key Laboratory of Precision Medicine for Malignant Tumors, Shenyang, Liaoning, 110042, People's Republic of China.
  • 5. Faculty of Medicine, Dalian University of Technology, Dalian, Liaoning, 116024, People's Republic of China.
  • 6. Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People's Republic of China.
  • # Contributed equally.
PMID: 39902066 DOI: 10.2147/IJN.S478435
Abstract

Purpose: Phototherapy has remarkable advantages in Cancer treatment, owing to its high efficiency and minimal invasiveness. Indocyanine green (ICG) plays an important role in photo-mediated therapy. However, it has several disadvantages such as poor stability in aqueous solutions, easy aggregation of molecules, and short plasma half-life. This study aimed to develop an efficient nanoplatform to enhance the effects of photo-mediated therapy.

Methods: We developed a novel bio-nanoplatform by integrating edible ginger-derived exosome-like nanoparticles (GDNPs) and the Photosensitizer, ICG (GDNPs@ICG). GDNPs were isolated from ginger juice and loaded with ICG by co-incubation. The size distribution, zeta potential, morphology, total lipid content, and drug release behavior of the GDNPs@ICG were characterized. The photothermal performance, cellular uptake and distribution, cytotoxicity, anti-tumor effects, and mechanism of action of GDNPs@ICG were investigated both in vitro and in vivo.

Results: GDNPs@ICG were taken up by tumor cells via a lipid-dependent pathway. When irradiated by an 808 nm NIR laser, GDNPs@ICG generated high levels of ROS, MDA, and local hyperthermia within the tumor, which caused lipid peroxidation and ER stress, thus enhancing the photo-mediated breast tumor therapy effect. Furthermore, in vivo studies demonstrated that engineered GDNPs@ICG significantly inhibited breast tumor growth and presented limited toxicity. Moreover, by detecting the expression of CD31, N-Cadherin, IL-6, IFN-γ, CD8, p16, p21, and p53 in tumor tissues, we found that GDNPs@ICG substantially reduced angiogenesis, inhibited metastasis, activated the anti-tumor immune response, and promoted cell senescence in breast tumor.

Conclusion: Our study demonstrated that the novel bio-nanoplatform GDNPs@ICG enhanced the photo-mediated therapeutic effect in breast tumor. GDNPs@ICG could be an alternative for precise and efficient anti-tumor phototherapy.

Keywords
ER stress; ginger-derived exosome-like nanoparticles; indocyanine green; lipid peroxidation; phototherapy.
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