Nano-Gene and Drug Delivery Group, Discipline of Biochemistry, School of Life Sciences, University of Kwa-Zulu Natal, Private Bag X54001, Durban, South Africa.
Curr Med Chem. 2020;27(33):5480-5509. doi: 10.2174/0929867326666191125092111.
Over the past decade, there has been a surge in the number of mitochondrialactive therapeutics for conditions ranging from cancer to aging. Subcellular targeting interventions can modulate adverse intracellular processes unique to the compartments within the cell. However, there is a dearth of reviews focusing on mitochondrial nano-delivery, and this review seeks to fill this gap with regards to nanotherapeutics of the mitochondria.
Besides its potential for a higher therapeutic index than targeting at the tissue and cell levels, subcellular targeting takes into account the limitations of systemic drug administration and significantly improves pharmacokinetics. Hence, an extensive literature review was undertaken and salient information was compiled in this review.
From literature, it was evident that nanoparticles with their tunable physicochemical properties have shown potential for efficient therapeutic delivery, with several nanomedicines already approved by the FDA and others in clinical trials. However, strategies for the development of nanomedicines for subcellular targeting are still emerging, with an increased understanding of dysfunctional molecular processes advancing the development of treatment modules. For optimal delivery, the design of an ideal carrier for subcellular delivery must consider the features of the diseased microenvironment. The functional and structural features of the mitochondria in the diseased state are highlighted and potential nano-delivery interventions for treatment and diagnosis are discussed.
This review provides an insight into recent advances in subcellular targeting, with a focus on en route barriers to subcellular targeting. The impact of mitochondrial dysfunction in the aetiology of certain diseases is highlighted, and potential therapeutic sites are identified.
在过去的十年中，针对癌症到衰老等各种病症的线粒体活性治疗药物的数量激增。亚细胞靶向干预可以调节细胞内特有的不利的细胞内过程。然而，目前缺乏专门针对线粒体纳米递药的综述，因此本文旨在填补这一空白。
除了比组织和细胞水平靶向具有更高的治疗指数的潜力外，亚细胞靶向还考虑了系统药物给药的局限性，并显著改善了药代动力学。因此，我们进行了广泛的文献综述，并在本文中汇编了相关的重要信息。
从文献中可以明显看出，具有可调物理化学性质的纳米颗粒显示出高效治疗药物输送的潜力，已有几种纳米药物已获得 FDA 的批准，还有一些正在临床试验中。然而，用于亚细胞靶向的纳米药物的开发策略仍在不断涌现，对功能失调的分子过程的深入了解促进了治疗模块的发展。为了实现最佳的输送效果，用于亚细胞输送的理想载体的设计必须考虑到病变微环境的特点。本文强调了病变状态下线粒体的功能和结构特征，并讨论了潜在的纳米药物干预治疗和诊断的应用。
本文综述了亚细胞靶向的最新进展，重点介绍了亚细胞靶向的途径障碍。本文还强调了线粒体功能障碍在某些疾病发病机制中的作用，并确定了潜在的治疗靶点。
