Al Tahan Mohamad Anas, Al Tahan Sana
Aston Medical Research Institute, College of Health and Life Sciences, Aston University, Birmingham, United Kingdom.
Faculty of Pharmacy, Arab International University, Daraa, Syria.
Br J Biomed Sci. 2024 Nov 18;81:13707. doi: 10.3389/bjbs.2024.13707. eCollection 2024.
Mitochondria, known as the cell's powerhouse, play a critical role in energy production, cellular maintenance, and stemness regulation in non-cancerous cells. Despite their importance, using drug delivery systems to target the mitochondria presents significant challenges due to several barriers, including cellular uptake limitations, enzymatic degradation, and the mitochondrial membranes themselves. Additionally, barriers in the organs to be targetted, along with extracellular barriers formed by physiological processes such as the reticuloendothelial system, contribute to the rapid elimination of nanoparticles designed for mitochondrial-based drug delivery. Overcoming these challenges has led to the development of various strategies, such as molecular targeting using cell-penetrating peptides, genomic editing, and nanoparticle-based systems, including porous carriers, liposomes, micelles, and Mito-Porters. Porous carriers stand out as particularly promising candidates as drug delivery systems for targeting the mitochondria due to their large pore size, surface area, and ease of functionalisation. Depending on the pore size, they can be classified as micro-, meso-, or macroporous and are either ordered or non-ordered based on both size and pore uniformity. Several methods are employed to target the mitochondria using porous carriers, such as surface modifications with polyethylene glycol (PEG), incorporation of targeting ligands like triphenylphosphonium, and capping the pores with gold nanoparticles or chitosan to enable controlled and triggered drug delivery. Photodynamic therapy is another approach, where drug-loaded porous carriers generate reactive oxygen species (ROS) to enhance mitochondrial targeting. Further advancements have been made in the form of functionalised porous silica and carbon nanoparticles, which have demonstrated potential for effective drug delivery to mitochondria. This review highlights the various approaches that utilise porous carriers, specifically focusing on silica-based systems, as efficient vehicles for targeting mitochondria, paving the way for improved drug delivery strategies in mitochondrial therapies.
线粒体被称为细胞的“动力源”，在非癌细胞的能量产生、细胞维持和干性调节中发挥着关键作用。尽管它们很重要，但由于存在多种障碍，包括细胞摄取限制、酶降解以及线粒体膜本身，使用药物递送系统靶向线粒体面临重大挑战。此外，靶器官中的障碍以及由网状内皮系统等生理过程形成的细胞外障碍，会导致用于基于线粒体的药物递送的纳米颗粒迅速被清除。克服这些挑战促使人们开发了各种策略，例如使用细胞穿透肽的分子靶向、基因组编辑以及基于纳米颗粒的系统，包括多孔载体、脂质体、胶束和线粒体转运体。多孔载体作为靶向线粒体的药物递送系统脱颖而出，因为它们具有大孔径、高表面积且易于功能化。根据孔径大小，它们可分为微孔、介孔或大孔，并且根据大小和孔均匀性可分为有序或无序。使用多孔载体靶向线粒体有几种方法，例如用聚乙二醇（PEG）进行表面修饰、掺入三苯基膦等靶向配体，以及用金纳米颗粒或壳聚糖封端孔以实现可控和触发式药物递送。光动力疗法是另一种方法，载药多孔载体可产生活性氧（ROS）以增强线粒体靶向性。功能化多孔二氧化硅和碳纳米颗粒形式的进一步进展已证明其在向线粒体有效递送药物方面的潜力。本综述重点介绍了利用多孔载体的各种方法，特别关注基于二氧化硅的系统，作为靶向线粒体的有效载体，为线粒体治疗中改进药物递送策略铺平道路。
