肿瘤的代谢重编程:诱导免疫抑制和纳米级药物输送系统的治疗前景。

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Qianwen Li, Fansu Meng, Lina Yang, Alicia Marcelina Díaz García, Marina Parkhats, Jaiwoo Lee, Kosuke Kusamori, Makiya Nishikawa, Honghui Gu, Qi Li, Gareth R. Williams*, Zhenjiang Yang* and Yu Cai*, 
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引用次数: 0

摘要

肿瘤的发生、发展和转移都伴随着代谢重编程。在肿瘤免疫微环境(TIME)中,肿瘤细胞代谢改变的影响常常被忽视,导致治疗失败。在现实中,肿瘤细胞和免疫细胞在时间内竞争营养物质,诱发缺氧、酸中毒和其他条件,共同促进免疫抑制微环境。针对代谢重编程的治疗策略对癌症治疗有很大的希望。本文系统回顾了肿瘤代谢重编程与TIME之间的相互作用,重点讨论了代谢重编程介导免疫抑制的机制。它强调了纳米级递送系统通过代谢物递送来调节免疫细胞的策略,包括不同的载体平台(例如,脂质体和聚合物),主动靶向优化(例如,配体-受体相互作用),刺激反应释放(例如,pH/活性氧(ROS)触发系统),以及多模式协同治疗(例如,光疗结合代谢抑制剂)。所有这些都旨在重塑肿瘤和免疫细胞之间的代谢平衡。此外,讨论还包括代谢重编程驱动的免疫抑制,通过代谢干预逆转免疫抑制的纳米级系统的设计策略,以及临床翻译。最后,展望了代谢靶向纳米药物递送系统在肿瘤治疗中的应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Metabolic Reprogramming of Tumors: Induced Immunosuppression and Therapeutic Prospects of Nanoscale Drug Delivery Systems

Metabolic Reprogramming of Tumors: Induced Immunosuppression and Therapeutic Prospects of Nanoscale Drug Delivery Systems

The initiation, progression, and metastasis of tumors are accompanied by metabolic reprogramming. Within the tumor immune microenvironment (TIME), the impact of metabolic alterations in tumor cells is often overlooked, leading to therapeutic failure. In reality, tumor cells and immune cells within TIME compete for nutrients, inducing hypoxia, acidosis, and other conditions that collectively foster an immunosuppressive microenvironment. Therapeutic strategies targeting metabolic reprogramming hold great promise for cancer treatment. This account systematically reviews the interplay between tumor metabolic reprogramming and the TIME, focusing on the mechanisms by which metabolic reprogramming mediates immune suppression. It highlights the strategies of nanoscale delivery systems to regulate immune cells through metabolite delivery, including diverse carrier platforms (e.g., liposomes and polymers), active targeting optimization (e.g., ligand–receptor interactions), stimuli-responsive release (e.g., pH/reactive oxygen species (ROS)-triggered systems), and multimodal synergistic therapies (e.g., phototherapy combined with metabolic inhibitors), all aimed at reshaping the metabolic balance between tumor and immune cells. Additionally, the discussion encompasses metabolic reprogramming-driven immune suppression, design strategies for nanoscale systems to reverse immunosuppression via metabolic interventions, and clinical translation. Finally, the application prospects of metabolism-targeted nanodrug delivery systems in tumor therapy are envisioned.

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来源期刊
Molecular Pharmaceutics
Molecular Pharmaceutics 医学-药学
CiteScore
8.00
自引率
6.10%
发文量
391
审稿时长
2 months
期刊介绍: Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
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