Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

背景：在过去的十年中，针对从癌症到衰老的各种疾病的线粒体活性疗法的数量激增。亚细胞靶向干预可以调节不利于细胞内隔室的细胞内过程。然而，缺乏关于线粒体纳米递送的评论，并且该评论试图填补关于线粒体的纳米疗法的空白。

方法：亚细胞靶向除了具有比靶向组织和细胞水平更高的治疗指数潜力外，还考虑了全身性药物给药的局限性并显着改善了药代动力学。因此，进行了广泛的文献综述，并在该综述中汇编了重要信息。

结果：从文献中可以明显看出，具有可调节理化特性的纳米颗粒已显示出有效治疗递送的潜力，其中几种纳米药物已获得FDA和其他临床试验的批准。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，随着对功能障碍分子过程的更多了解促进了治疗模块的开发。为了获得最佳递送，用于亚细胞递送的理想载体的设计必须考虑患病微环境的特征。强调了患病线粒体的功能和结构特征，并讨论了用于治疗和诊断的潜在纳米传递干预措施。

结论：这篇综述提供了对亚细胞靶向的最新进展的见解，重点是亚细胞靶向的通路障碍。线粒体功能障碍在某些疾病的病因学中的影响突出，并确定了潜在的治疗部位。