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

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.