State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China.
Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, 300100, China.
J Nanobiotechnology. 2024 Sep 5;22(1):542. doi: 10.1186/s12951-024-02813-w.
Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What's more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment.
光疗是一种很有前途的抗肿瘤方式，包括光热疗法（PTT）和光动力疗法（PDT）。然而，肿瘤局部缺氧、肿瘤细胞中吲哚胺 2,3-双加氧酶（IDO）和程序性细胞死亡配体 1（PD-L1）的过表达极大地限制了光疗的疗效。为了解决这些问题，开发了自组装多功能聚合物胶束（RIMNA）来共递送光敏剂吲哚菁绿（ICG）、氧合剂 MnO、IDO 抑制剂 NLG919 和 Toll 样受体 4 激动剂单磷酰脂质 A（MPLA）。值得注意的是，RIMNA 聚合物胶束具有良好的稳定性、均匀的形态、优异的生物相容性和增强的 PTT/PDT 效果。更重要的是，RIMNA 介导的 IDO 抑制与程序性死亡受体-1（PD-1）/PD-L1 阻断相结合，显著改善了免疫抑制作用，并促进了免疫激活。基于 RIMNA 的光免疫疗法与 PD-1 抗体协同作用，可显著抑制原代肿瘤的增殖，并刺激免疫功能，从而极大地抑制肺转移和远处肿瘤的生长。本研究提供了一种有效增强光疗疗效和减轻免疫抑制的方法，从而为癌症治疗带来临床获益。
