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基于三苯基膦的线粒体靶向纳米载体:推进癌症治疗

Triphenylphosphine-Based Mitochondrial Targeting Nanocarriers: Advancing Cancer Therapy.

作者信息

Ali Mohd Shoab, Gowda B H Jaswanth, Shukla Rahul, Kesharwani Prashant

机构信息

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.

Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to be University), Mangalore, KA, 575018, India.

出版信息

Clin Pharmacol. 2025 Jun 10;17:119-141. doi: 10.2147/CPAA.S526895. eCollection 2025.

Abstract

Numerous chemotherapeutic drugs are commercially available for cancer treatment; however, their efficacy is often compromised by diminishing therapeutic effectiveness and unpredictable adverse effects. The lack of specific targeting limits their optimal therapeutic potential. Mitochondria are the primary sites of cellular energy production and play a critical role in cell survival and death. Furthermore, numerous studies have found an apparent association between mitochondrial metabolism and carcinogenesis and progression. Therefore, significant attention has been directed toward nanocarriers specifically designed for mitochondrial delivery, aiming to enhance the precision of chemotherapeutic agent transport to these critical organelles. Among these, triphenylphosphonium has emerged as a prominent mitochondrial targeting agent due to its superior targeting capabilities. This approach not only reduces the required drug dosage but also minimizes adverse effects on healthy tissues. This review provides a concise analysis of nanotechnology's contributions to cancer therapy, emphasizing its potential for targeting at both cellular and sub-cellular levels. Additionally, it delves into mitochondrial targeting, with a particular focus on nanocarriers engineered for efficient mitochondrial drug delivery. Moreover, it focuses on strategies employed by researchers to introduce TPP in nanocarrier systems for mitochondrial delivery and concludes by addressing challenges associated with TPP including hemolytic activity and how researchers mitigate this issue.

摘要

目前有多种化疗药物可用于癌症治疗;然而,它们的疗效常常因治疗效果的降低和不可预测的副作用而受到影响。缺乏特异性靶向限制了它们的最佳治疗潜力。线粒体是细胞能量产生的主要场所,在细胞存活和死亡中起着关键作用。此外,大量研究发现线粒体代谢与癌症发生和进展之间存在明显关联。因此,人们将大量注意力投向了专门设计用于线粒体递送的纳米载体,旨在提高化疗药物向这些关键细胞器运输的精确性。其中,三苯基膦由于其卓越的靶向能力已成为一种突出的线粒体靶向剂。这种方法不仅减少了所需的药物剂量,还将对健康组织的副作用降至最低。本综述简要分析了纳米技术对癌症治疗的贡献,强调了其在细胞和亚细胞水平靶向的潜力。此外,还深入探讨了线粒体靶向,特别关注为高效线粒体药物递送而设计的纳米载体。此外,重点介绍了研究人员在纳米载体系统中引入三苯基膦以实现线粒体递送所采用的策略,并通过解决与三苯基膦相关的挑战(包括溶血活性)以及研究人员如何缓解这一问题来得出结论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2e1/12168994/1f2b2ab3bc46/CPAA-17-119-g0001.jpg

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