线粒体靶向纳米颗粒(mitoNANO):一种新兴的癌症治疗捷径

Q3 Biochemistry, Genetics and Molecular Biology Biomaterials and biosystems Pub Date : 2021-09-01 DOI:10.1016/j.bbiosy.2021.100023
Tanveer A. Tabish , Michael R. Hamblin
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引用次数: 18

摘要

早期对线粒体的理解假设它们是“无辜的细胞器”,只致力于能量的生产和利用。有趣的是,最近的研究结果详细概述了“现代”观点,即线粒体是一个重要但未被重视的药物靶点。线粒体与许多人类疾病的病理生理有关,从神经退行性疾病、心血管疾病到感染和癌症。现在很清楚,正常的线粒体功能涉及到细胞产生脂质、蛋白质和核酸的构建块,从而促进细胞生长。另一方面,线粒体功能障碍将关键的细胞功能重新编程为病理途径,并被认为是癌症的一个完整标志。因此,靶向线粒体的策略可以通过克服与传统药物相关的一些问题,包括低溶解度,生物利用度差和非选择性生物分布,为对抗癌症提供丰富的新治疗方法。纳米粒子与“经典”化疗药物的结合创造了生物相容性的、多功能的线粒体靶向纳米平台,这是最近的研究。这种方法现在正在迅速扩展到靶向药物输送系统,以及可以用光激活的混合纳米结构(光动力和/或光热疗法)。选择性地将纳米颗粒递送到线粒体是一种更有选择性、更有针对性和更安全的癌症治疗的优雅捷径。我们建议使用纳米颗粒靶向线粒体被称为“mitoNANO”。本文综述了mitoNANO作为晚期癌症治疗药物的设计和应用,以克服耐药和减少副作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Mitochondria-targeted nanoparticles (mitoNANO): An emerging therapeutic shortcut for cancer

The early understanding of mitochondria posited that they were ‘innocent organelles’ solely devoted to energy production and utilisation. Intriguingly, recent findings have outlined in detail the ‘modern-day’ view that mitochondria are an important but underappreciated drug target. Mitochondria have been implicated in the pathophysiology of many human diseases, ranging from neurodegenerative disorders and cardiovascular diseases to infections and cancer. It is now clear that normal mitochondrial function involves the building blocks of a cell to generate lipids, proteins and nucleic acids thereby facilitating cell growth. On the other hand, mitochondrial dysfunction reprograms crucial cellular functions into pathological pathways, and is considered as an integral hallmark of cancer. Therefore, strategies to target mitochondria can provide a wealth of new therapeutic approaches in the fight against cancer, by overcoming a number of problems associated with conventional pharmaceutical drugs, including low solubility, poor bioavailability and non-selective biodistribution. The combination of nanoparticles with ‘classical’ chemotherapeutic drugs to create biocompatible, multifunctional mitochondria-targeted nanoplatforms has been recently studied. This approach is now rapidly expanding for targeted drug delivery systems, and for hybrid nanostructures that can be activated with light (photodynamic and/or photothermal therapy). The selective delivery of nanoparticles to mitochondria is an elegant shortcut to more selective, targeted, and safer cancer treatment. We propose that the use of nanoparticles to target mitochondria be termed “mitoNANO”. The present minireview sheds light on the design and application of mitoNANO as advanced cancer therapeutics, that may overcome drug resistance and show fewer side effects.

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