Sun Changzhen, He Qingqing, Yang Xun, Wang Jianv, Xia Dengmei, Xia Tong, Liao Hongye, Xiong Xia, Liao Yongmei, Shen Hongping, Sun Qin, Yuan Yuan, He Yuanmin, Liu Li
Drug Research Center of Integrated Traditional Chinese and Western Medicine, Luzhou Key Laboratory of Research and Development of Medical Institution Preparations and Large-scale Health Products, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China.
Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China.
Colloids Surf B Biointerfaces. 2025 Jul;251:114565. doi: 10.1016/j.colsurfb.2025.114565. Epub 2025 Feb 19.
Phototherapy is a treatment method that uses the characteristics of different bands of light to treat diseases. Tumor immunotherapy, on the other hand, treats tumors by regulating the body's immune system. The combination of phototherapy and immunotherapy can significantly enhance the treatment of melanoma. In this study, we prepared and characterized INEs, a novel ethosome composed of the photosensitizer IR251 and the Indoleamine-2, 3-dioxygenase (IDO) inhibitor NLG919. INEs demonstrated excellent phototherapeutic properties, strong phototoxicity, and a notable ability to inhibit IDO. Under 808 nm laser irradiation, INEs effectively induced immunogenic cell death (ICD) in melanoma cells. In vivo experiments demonstrated that INEs injection into primary tumors triggered ICD, promoted maturation of DC cells, and activated naive T cells, leading to the production of effector T cells (specifically CD4 and CD8 T cells) that targeted and killed tumor cells. Both primary and distant tumors were treated simultaneously with favorable biosafety. In conclusion, INEs represent a promising strategy for melanoma treatment by a combination of phototherapy and immunotherapy with high safety. This study provides new insights and a theoretical basis for the clinical treatment of melanoma.
光疗是一种利用不同波段光的特性来治疗疾病的治疗方法。另一方面，肿瘤免疫疗法通过调节机体免疫系统来治疗肿瘤。光疗与免疫疗法相结合可显著增强黑色素瘤的治疗效果。在本研究中，我们制备并表征了INEs，这是一种由光敏剂IR251和吲哚胺-2,3-双加氧酶（IDO）抑制剂NLG919组成的新型醇质体。INEs表现出优异的光疗特性、强光毒性以及显著的抑制IDO的能力。在808 nm激光照射下，INEs能有效诱导黑色素瘤细胞发生免疫原性细胞死亡（ICD）。体内实验表明，将INEs注射到原发性肿瘤中可引发ICD，促进树突状细胞（DC）成熟，并激活初始T细胞，从而产生靶向并杀死肿瘤细胞的效应T细胞（特别是CD4和CD8 T细胞）。原发性肿瘤和远处肿瘤均可同时得到治疗，且具有良好的生物安全性。总之，INEs代表了一种通过光疗与免疫疗法相结合且安全性高的黑色素瘤治疗的有前景策略。本研究为黑色素瘤的临床治疗提供了新的见解和理论依据。
