Review

肿瘤免疫治疗中IDO1抑制剂的纳米递送优化：挑战与策略

Nanodelivery Optimization of IDO1 Inhibitors in Tumor Immunotherapy: Challenges and Strategies

International Journal of Nanomedicine

影响因子:6.5

分区:医学2区 / 药学2区纳米科技3区

发表日期:2024

作者: Kehua Jiang, Qing Wang, Xiao-Long Chen, Xiaodong Wang, Xiaoya Gu, Shuangshuang Feng, Jian Wu, Haojie Shang, Xiaozhuo Ba, Yanlong Zhang, Kun Tang

DOI: 10.2147/IJN.S458086

摘要

色氨酸（Trp）代谢在癌症免疫中起着关键作用。吲哚胺2,3-双加氧酶1（IDO1）是Trp代谢途径中的关键酶，通过该途径Trp被降解为犬尿氨酸（Kyn）。IDO1介导的Trp代谢物可以抑制肿瘤免疫，促进癌细胞的免疫逃逸；因此，靶向IDO1是潜在的肿瘤免疫治疗策略。近年来，许多IDO1抑制剂作为免疫治疗药物进入临床试验，但其存在口服生物利用度低、起效慢和高毒性等缺点。随着纳米技术的不断发展，药物逐步进入精准医疗时代。无机、脂质和聚合物纳米颗粒（NPs）载药的纳米药物在肿瘤治疗中展现出巨大潜力，为克服肿瘤多样性和提高治疗效果提供了新途径。相比传统药物，纳米药物具有延长半衰期、低毒性、靶向递送和响应性释放等显著优势。此外，基于这些纳米材料的物理化学特性（如光热、超声响应和化学催化特性），开发了多种联合治疗策略，以协同增强IDO1抑制剂的抗癌效果。本综述概述了Trp-IDO1-Kyn途径在肿瘤免疫逃逸中的作用机制，讨论了IDO1抑制剂的分类、临床应用及转化开发中的障碍，总结了基于IDO1抑制剂的纳米药物递送系统作为联合治疗策略的应用，并阐述了其临床应用中面临的问题。我们期望本综述能为开发能克服当前治疗局限、提升癌症免疫治疗效果的IDO1抑制剂纳米药物提供指导，推动肿瘤免疫治疗的新突破。

Abstract

Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy.