Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China.
Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea.
Biomaterials. 2019 Aug;211:25-47. doi: 10.1016/j.biomaterials.2019.05.002. Epub 2019 May 3.
Lysosomes, an important organelle of eukaryotic cells, are covered with the cell membrane and contain an array of degradative enzymes. The disrupt in lysosomal functions may lead to the development of severe diseases. In nanotechnology, nanomaterials working mechanism and its biomedical output are highly dependent on the lysosomes as it plays a crucial role in intracellular transport. Several nanomaterials specifically designed for lysosome-related actions are highly advantageous in trafficking and delivering the loaded imaging/therapeutic agents. But for other applications, especially gene-based therapeutic delivery into the sub-organelles such as mitochondria and nucleus, lysosomal related degradation could be an obstacle to achieve a maximal therapeutic index. In order to understand the relationship between lysosomes and designed nanomaterials for kind of desired application in biomedical research, complete knowledge of their various designing strategies, size dependent or ligand supportive cellular uptake mechanisms, trafficking, and localizations in eukaryotic cells is highly desired. In this review, we intended to discuss various nanomaterial types that have been applied in biomedical applications based on lysosomal internalization and escape from endo/lysosomes and explored their related advantages/disadvantages. Additionally, we also deliberated nanomaterials direct translocation mechanism, their autophagic accumulation and the underlying mechanism to induced autophagy. Finally, some challenges and critical issues in current research from clinical application perspective has also been addressed. Great understanding of these factors will help in understanding and facilitating the development of safe and effective lysosomal related nanomaterial-based imaging/therapeutic systems for future applications.
溶酶体是真核细胞的一种重要细胞器,被细胞膜所包裹,其中含有一系列的降解酶。溶酶体功能的破坏可能导致严重疾病的发生。在纳米技术中,纳米材料的作用机制及其生物医学应用输出高度依赖于溶酶体,因为它在细胞内运输中起着至关重要的作用。一些专门设计用于溶酶体相关作用的纳米材料在运输和递送至负载的成像/治疗剂方面具有很大的优势。但对于其他应用,特别是基因治疗递送至亚细胞器(如线粒体和细胞核),溶酶体相关降解可能是实现最大治疗指数的障碍。为了了解溶酶体与用于生物医学研究中某种预期应用的设计纳米材料之间的关系,需要全面了解它们的各种设计策略、基于尺寸或配体支持的细胞摄取机制、运输和在真核细胞中的定位。在这篇综述中,我们旨在讨论已经应用于生物医学应用的各种纳米材料类型,这些纳米材料基于溶酶体的内吞作用和从内体/溶酶体中逃逸,并探讨了它们的相关优缺点。此外,我们还讨论了纳米材料的直接转位机制、自噬积累及其诱导自噬的潜在机制。最后,还从临床应用的角度讨论了当前研究中的一些挑战和关键问题。深入了解这些因素将有助于理解和促进基于安全有效的溶酶体相关纳米材料的成像/治疗系统的发展,以满足未来的应用需求。