Unlocking the Mitochondria for Nanomedicine-based Treatments: Overcoming Biological Barriers, Improving Designs, and Selecting Verification Techniques

IF 15.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Camilla Pegoraro, Inés Domingo-Ortí, Inmaculada Conejos-Sánchez, María J. Vicent
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Abstract

Enhanced targeting approaches will support the treatment of diseases associated with dysfunctional mitochondria, which play critical roles in energy generation and cell survival. Obstacles to mitochondria-specific targeting include the presence of distinct biological barriers and the need to pass through (or avoid) various cell internalization mechanisms. A range of studies have reported the design of mitochondrially-targeted nanomedicines that navigate the complex routes required to influence mitochondrial function; nonetheless, a significant journey lies ahead before mitochondrially-targeted nanomedicines become suitable for clinical use. Moving swiftly forward will require safety studies, in vivo assays confirming effectiveness, and methodologies to validate mitochondria-targeted nanomedicines' subcellular location/activity. From a nanomedicine standpoint, we describe the biological routes involved (from administration to arrival within the mitochondria), the features influencing rational design, and the techniques used to identify/validate successful targeting. Overall, rationally-designed mitochondria-targeted-based nanomedicines hold great promise for precise subcellular therapeutic delivery.

Abstract Image

Abstract Image

释放线粒体,实现基于纳米药物的治疗:克服生物学障碍、改进设计和选择验证技术
线粒体在能量生成和细胞存活中发挥着关键作用,增强靶向方法将有助于治疗与线粒体功能障碍有关的疾病。线粒体特异性靶向的障碍包括存在不同的生物屏障以及需要通过(或避免)各种细胞内化机制。一系列研究已经报道了线粒体靶向纳米药物的设计,这些药物可以通过影响线粒体功能所需的复杂途径;然而,在线粒体靶向纳米药物适合临床使用之前,还有很长的路要走。要想迅速取得进展,就需要进行安全性研究、体内试验以确认有效性,以及验证线粒体靶向纳米药物亚细胞位置/活性的方法。从纳米药物的角度来看,我们描述了所涉及的生物途径(从给药到到达线粒体内)、影响合理设计的特征以及用于识别/验证成功靶向的技术。总之,合理设计的线粒体靶向纳米药物在亚细胞精确给药方面大有可为。
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来源期刊
CiteScore
28.10
自引率
5.00%
发文量
294
审稿时长
15.1 weeks
期刊介绍: The aim of the Journal is to provide a forum for the critical analysis of advanced drug and gene delivery systems and their applications in human and veterinary medicine. The Journal has a broad scope, covering the key issues for effective drug and gene delivery, from administration to site-specific delivery. In general, the Journal publishes review articles in a Theme Issue format. Each Theme Issue provides a comprehensive and critical examination of current and emerging research on the design and development of advanced drug and gene delivery systems and their application to experimental and clinical therapeutics. The goal is to illustrate the pivotal role of a multidisciplinary approach to modern drug delivery, encompassing the application of sound biological and physicochemical principles to the engineering of drug delivery systems to meet the therapeutic need at hand. Importantly the Editorial Team of ADDR asks that the authors effectively window the extensive volume of literature, pick the important contributions and explain their importance, produce a forward looking identification of the challenges facing the field and produce a Conclusions section with expert recommendations to address the issues.
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