IDO1抑制剂在肿瘤免疫疗法中的纳米传递优化：挑战和策略
Nanodelivery Optimization of IDO1 Inhibitors in Tumor Immunotherapy: Challenges and Strategies
影响因子:6.50000
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
摘要
色氨酸（TRP）代谢在癌症免疫中起着至关重要的作用。吲哚胺2.3-二加氧酶1（IDO1）是代谢途径中的至关重要酶，TRP降解为kynurenine（Kyn）。 IDO1介导的TRP代谢产物可以抑制肿瘤免疫力并促进癌细胞免疫逃避。因此，靶向IDO1是一种潜在的肿瘤免疫疗法策略。最近，已将许多IDO1抑制剂引入临床试验中，作为用于癌症治疗的免疫治疗剂。但是，诸如低口服生物利用度，作用缓慢和高毒性等缺点与这些药物有关。随着纳米技术的持续发展，医学逐渐进入了精确的医疗时代。无机，脂质和聚合物纳米颗粒（NPS）携带的纳米果显示出巨大的肿瘤治疗潜力，提供了克服肿瘤多样性并提高治疗功效的新方法。与传统药物相比，纳米医学具有许多重要的优势，包括长时间的半衰期，低毒性，有针对性的递送和响应良好的释放。此外，基于这些纳米材料的物理化学特性（例如光热，超声反应和化学催化特性），已经开发出各种组合治疗策略来协同IDO1抑制剂的影响并增强其抗癌功效。这篇综述是对TRP-IDO1-KYN途径在肿瘤免疫逃生中起作用的机制的概述。总结了IDO1抑制剂的分类，其临床应用和翻译发展的障碍，总结了基于IDO1抑制剂的纳米糖递送系统作为组合治疗策略的使用，并阐明了其临床应用中面临的问题。我们预计，这项综述将为IDO1抑制剂基于IDO1的纳米纳米医学的发展提供指导，这些纳米粒纳米医学可以克服当前治疗的局限性，提高癌症免疫疗法的疗效并在癌症免疫疗法领域带来新的突破。
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.