基于脂质的纳米药物(LBNMs),包括脂质体,脂质纳米颗粒(LNP)和细胞外囊泡(EV),被认为是临床上最可接受的纳米制剂之一。然而,工作台到床边的翻译效率远远不能令人满意,主要是由于在单粒子水平上缺乏对其物理和生化属性的深入了解。在这次审查中,我们首先简要介绍了LBNMs,突出了过去几十年来的一些里程碑和相关的科学和临床成就,以及LBNM表征方面的巨大挑战。接下来,我们概述了LBNMs的每个类别以及在很大程度上决定其生物学特性和临床表现的核心特性,例如大小分布,颗粒浓度,形态学,药物封装和表面性能。然后,包括电子显微镜在内的几种分析技术的最新应用,原子力显微镜,荧光显微镜,拉曼显微术,纳米粒子跟踪分析,全面讨论了可调谐电阻脉冲传感和流式细胞术对LBNM单粒子表征的影响。特别是,强调了新开发的纳米流式细胞术的相对优势,该技术可以对小于40nm的LBNM的物理和生化特性进行定量分析,并具有高通量和统计稳健性。这篇综述文章的总体目标是说明其重要性,与LBNM单粒子表征相关的挑战和成就。
Lipid-based nanomedicines (LBNMs), including liposomes, lipid nanoparticles (LNPs) and extracellular vesicles (EVs), are recognized as one of the most clinically acceptable nano-formulations. However, the bench-to-bedside translation efficiency is far from satisfactory, mainly due to the lack of in-depth understanding of their physical and biochemical attributes at the single-particle level. In this review, we first give a brief introduction of LBNMs, highlighting some milestones and related scientific and clinical achievements in the past several decades, as well as the grand challenges in the characterization of LBNMs. Next, we present an overview of each category of LBNMs as well as the core properties that largely dictate their biological characteristics and clinical performance, such as size distribution, particle concentration, morphology, drug encapsulation and surface properties. Then, the recent applications of several analytical techniques including electron microscopy, atomic force microscopy, fluorescence microscopy, Raman microscopy, nanoparticle tracking analysis, tunable resistive pulse sensing and flow cytometry on the single-particle characterization of LBNMs are thoroughly discussed. Particularly, the comparative advantages of the newly developed nano-flow cytometry that enables quantitative analysis of both the physical and biochemical characteristics of LBNMs smaller than 40 nm with high throughput and statistical robustness are emphasized. The overall aim of this review article is to illustrate the importance, challenges and achievements associated with single-particle characterization of LBNMs.