Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou, People's Republic of China.
Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, People's Republic of China.
Int J Nanomedicine. 2023 Jun 7;18:3021-3033. doi: 10.2147/IJN.S414117. eCollection 2023.
Photothermal therapy (PTT) is a promising anticancer treatment that involves inducing thermal ablation and enhancing antitumor immune responses. However, it is difficult to completely eradicate tumor foci through thermal ablation alone. Additionally, the PTT elicited antitumor immune responses are often insufficient to prevent tumor recurrence or metastasis, due to the presence of an immunosuppressive microenvironment. Therefore, combining photothermal and immunotherapy is believed to be a more effective treatment approach as it can modulate the immune microenvironment and amplify the post-ablation immune response.
Herein, the indoleamine 2, 3-dioxygenase-1 inhibitors (1-MT) loaded copper (I) phosphide nanocomposites (CuP/1-MT NPs) are prepared for PTT and immunotherapy. The thermal variations of the CuP/1-MT NPs solution under different conditions were measured. The cellular cytotoxicity and immunogenic cell death (ICD) induction efficiency of CuP/1-MT NPs were analyzed by cell counting kit-8 assay and flow cytometry in 4T1 cells. And the immune response and antitumor therapeutic efficacy of CuP/1-MT NPs were evaluated in 4T1-tumor bearing mice.
Even at low energy of laser irradiation, CuP/1-MT NPs remarkably enhanced PTT efficacy and induced immunogenic tumor cell death. Particularly, the tumor-associated antigens (TAAs) could help promote the maturation of dendritic cells (DCs) and antigen presentation, which further activates infiltration of CD8 T cells through synergistically inhibiting the indoleamine 2, 3-dioxygenase-1. Additionally, CuP/1-MT NPs decreased the suppressive immune cells such as regulatory T cells (Tregs) and M2 macrophages, indicating an immune suppression modulation effect.
CuP/1-MT nanocomposites with excellent photothermal conversion efficiency and immunomodulatory properties were prepared. In addition to enhanced the PTT efficacy and induced immunogenic tumor cell death, it also modulated the immunosuppressive microenvironment. Thereby, this study is expected to offer a practical and convenient approach to amplify the antitumor therapeutic efficiency with photothermal-immunotherapy.
光热疗法（PTT）是一种很有前途的癌症治疗方法，它涉及诱导热消融和增强抗肿瘤免疫反应。然而，仅通过热消融很难完全根除肿瘤病灶。此外，由于存在免疫抑制微环境，PTT 引发的抗肿瘤免疫反应往往不足以防止肿瘤复发或转移。因此，光热和免疫治疗相结合被认为是一种更有效的治疗方法，因为它可以调节免疫微环境并放大消融后的免疫反应。
在此，制备了负载吲哚胺 2,3-双加氧酶-1 抑制剂（1-MT）的铜（I）磷化纳米复合材料（CuP/1-MT NPs）用于 PTT 和免疫治疗。测量了 CuP/1-MT NPs 溶液在不同条件下的热变化。通过细胞计数试剂盒-8 测定法和流式细胞术在 4T1 细胞中分析了 CuP/1-MT NPs 的细胞毒性和免疫原性细胞死亡（ICD）诱导效率。并在 4T1 荷瘤小鼠中评估了 CuP/1-MT NPs 的免疫反应和抗肿瘤治疗效果。
即使在低能量的激光照射下，CuP/1-MT NPs 也显著增强了 PTT 疗效并诱导了免疫原性肿瘤细胞死亡。特别是肿瘤相关抗原（TAAs）有助于促进树突状细胞（DCs）的成熟和抗原呈递，通过协同抑制吲哚胺 2,3-双加氧酶-1，进一步激活 CD8 T 细胞的浸润。此外，CuP/1-MT NPs 减少了抑制性免疫细胞，如调节性 T 细胞（Tregs）和 M2 巨噬细胞，表明具有免疫抑制调节作用。
制备了具有优异光热转换效率和免疫调节性能的 CuP/1-MT 纳米复合材料。除了增强 PTT 疗效和诱导免疫原性肿瘤细胞死亡外，它还调节了免疫抑制微环境。因此，本研究有望提供一种实用且方便的方法，通过光热免疫治疗来放大抗肿瘤治疗效果。
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