Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL), 85764, Munich, Germany.
Department of Forensic Pathology, West China School of Preclinical and Forensic Medicine, Sichuan University, No. 17 Third Renmin Road North, Chengdu, 610041, China.
Adv Sci (Weinh). 2024 Apr;11(14):e2308659. doi: 10.1002/advs.202308659. Epub 2024 Jan 28.
Intracellular delivery of nano-drug-carriers (NDC) to specific cells, diseased regions, or solid tumors has entered the era of precision medicine that requires systematic knowledge of nano-biological interactions from multidisciplinary perspectives. To this end, this review first provides an overview of membrane-disruption methods such as electroporation, sonoporation, photoporation, microfluidic delivery, and microinjection with the merits of high-throughput and enhanced efficiency for in vitro NDC delivery. The impact of NDC characteristics including particle size, shape, charge, hydrophobicity, and elasticity on cellular uptake are elaborated and several types of NDC systems aiming for hierarchical targeting and delivery in vivo are reviewed. Emerging in vitro or ex vivo human/animal-derived pathophysiological models are further explored and highly recommended for use in NDC studies since they might mimic in vivo delivery features and fill the translational gaps from animals to humans. The exploration of modern microscopy techniques for precise nanoparticle (NP) tracking at the cellular, organ, and organismal levels informs the tailored development of NDCs for in vivo application and clinical translation. Overall, the review integrates the latest insights into smart nanosystem engineering, physiological models, imaging-based validation tools, all directed towards enhancing the precise and efficient intracellular delivery of NDCs.
将纳米药物载体 (NDC) 递送到特定细胞、病变区域或实体瘤中的细胞内，已经进入了精准医学的时代，这需要从多学科的角度系统地了解纳米生物学相互作用。为此，本文首先概述了电穿孔、声穿孔、光穿孔、微流控输送和微注射等膜破坏方法，这些方法具有高通量和提高体外 NDC 传递效率的优点。阐述了 NDC 特性（包括粒径、形状、电荷、疏水性和弹性）对细胞摄取的影响，并综述了几种旨在体内进行分级靶向和递药的 NDC 系统。进一步探索了新兴的体外或体内人/动物衍生的病理生理模型，并强烈推荐将其用于 NDC 研究，因为它们可能模拟体内传递特征，并填补从动物到人类的转化差距。现代显微镜技术在细胞、器官和机体水平上对精确纳米颗粒 (NP) 跟踪的探索，为针对体内应用和临床转化的 NDC 量身定制的发展提供了信息。总的来说，本文综述整合了智能纳米系统工程、生理模型、基于成像的验证工具的最新见解，旨在提高 NDC 的精确和高效的细胞内传递。
