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癌症治疗中的脂质纳米囊泡:提高反义寡核苷酸的靶向性和稳定性

Lipid Nanovesicles in Cancer Treatment: Improving Targeting and Stability of Antisense Oligonucleotides.

作者信息

Ding Hui-Yan, Zhou Han, Jiang Yi, Chen Si-Si, Wu Xiao-Xia, Li Yang, Luo Jun, Zhang Peng-Fei, Ding Yi-Nan

机构信息

Department of Interventional Radiology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Zhejiang Key Laboratory of Imaging and Interventional Medicine, Hangzhou, Zhejiang, 310022, People's Republic of China.

Zhejiang Provincial Research Center for Innovative Technology and Equipment in Interventional Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, People's Republic of China.

出版信息

Drug Des Devel Ther. 2025 Feb 14;19:1001-1023. doi: 10.2147/DDDT.S507402. eCollection 2025.

Abstract

Cancer remains a leading cause of mortality worldwide, accounting for approximately 10 million deaths annually. Standard treatments, including surgery, radiotherapy, and chemotherapy, often result in damage to healthy cells and severe toxic side effects. In recent years, antisense technology therapeutics, which interfere with RNA translation through complementary base pairing, have emerged as promising approaches for cancer treatment. Despite the availability of various antisense oligonucleotide (ASO) drugs on the market, challenges such as poor active targeting and susceptibility to clearance by circulating enzymes remain. Compared with other delivery systems, lipid nanovesicle (LNV) delivery systems offer a potential solution that uniquely enhances ASO targeting and stability. Studies have shown that LNVs can increase the accumulation of ASOs in tumor sites several-fold, significantly reducing systemic toxic reactions and demonstrating increased therapeutic efficiency in preclinical models. Additionally, LNVs can protect ASOs from enzymatic degradation within the body, extending their half-life and thus enhancing their therapeutic effects. This paper provides a comprehensive review of recent examples and applications of LNV delivery of ASOs in cancer treatment, highlighting their unique functions and outcomes. Furthermore, this paper discusses the key challenges and potential impacts of this innovative approach to cancer therapy.

摘要

癌症仍然是全球主要的死亡原因,每年约有1000万人死于癌症。包括手术、放疗和化疗在内的标准治疗方法常常会对健康细胞造成损害,并产生严重的毒副作用。近年来,反义技术疗法通过互补碱基配对干扰RNA翻译,已成为有前景的癌症治疗方法。尽管市场上有各种反义寡核苷酸(ASO)药物,但仍存在诸如活性靶向性差和易被循环酶清除等挑战。与其他递送系统相比,脂质纳米囊泡(LNV)递送系统提供了一种潜在的解决方案,能独特地增强ASO的靶向性和稳定性。研究表明,LNV可使ASO在肿瘤部位的蓄积增加数倍,显著降低全身毒性反应,并在临床前模型中显示出提高的治疗效果。此外,LNV可保护ASO在体内不被酶降解,延长其半衰期,从而增强其治疗效果。本文全面综述了LNV递送ASO在癌症治疗中的最新实例和应用,突出了它们独特的功能和效果。此外,本文还讨论了这种创新癌症治疗方法的关键挑战和潜在影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa51/11834698/6e1aa71e2140/DDDT-19-1001-g0001.jpg

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