Physical Chemistry 1, University of Lund, S-221 00 Lund, Sweden.
Consorzio Sistemi a Grande Interfase, Department of Chemistry, University of Florence, Sesto Fiorentino, Italy.
Adv Colloid Interface Sci. 2024 May;327:103156. doi: 10.1016/j.cis.2024.103156. Epub 2024 Apr 12.
Lipid-based nanoparticles (LNPs), ranging from nanovesicles to non-lamellar assemblies, have gained significant attention in recent years, as versatile carriers for delivering drugs, vaccines, and nutrients. Small-angle scattering methods, employing X-rays (SAXS) or neutrons (SANS), represent unique tools to unveil structure, dynamics, and interactions of such particles on different length scales, spanning from the nano to the molecular scale. This review explores the state-of-the-art on scattering methods applied to unveil the structure of lipid-based nanoparticles and their interactions with drugs and bioactive molecules, to inform their rational design and formulation for medical applications. We will focus on complementary information accessible with X-rays or neutrons, ranging from insights on the structure and colloidal processes at a nanoscale level (SAXS) to details on the lipid organization and molecular interactions of LNPs (SANS). In addition, we will review new opportunities offered by Time-resolved (TR)-SAXS and -SANS for the investigation of dynamic processes involving LNPs. These span from real-time monitoring of LNPs structural evolution in response to endogenous or external stimuli (TR-SANS), to the investigation of the kinetics of lipid diffusion and exchange upon interaction with biomolecules (TR-SANS). Finally, we will spotlight novel combinations of SAXS and SANS with complementary on-line techniques, recently enabled at Large Scale Facilities for X-rays and neutrons. This emerging technology enables synchronized multi-method investigation, offering exciting opportunities for the simultaneous characterization of the structure and chemical or mechanical properties of LNPs.
基于脂质的纳米粒子(LNPs),从纳米囊泡到非层状组装体,近年来受到了广泛关注,它们是递药、递疫苗和递营养物的多功能载体。小角散射方法,采用 X 射线(SAXS)或中子(SANS),是揭示这些粒子在不同长度尺度上的结构、动力学和相互作用的独特工具,涵盖从纳米到分子尺度。这篇综述探讨了应用散射方法揭示基于脂质的纳米粒子结构及其与药物和生物活性分子相互作用的最新进展,为其在医学应用中的合理设计和配方提供信息。我们将重点介绍 X 射线或中子可获得的互补信息,从纳米级水平的结构和胶体过程的见解(SAXS)到 LNPs 的脂质组织和分子相互作用的细节(SANS)。此外,我们将回顾时间分辨(TR)-SAXS 和 -SANS 为研究涉及 LNPs 的动态过程带来的新机会。这些机会包括实时监测 LNPs 结构响应内源性或外源性刺激的演变(TR-SANS),以及研究与生物分子相互作用时脂质扩散和交换的动力学(TR-SANS)。最后,我们将重点介绍 SAXS 和 SANS 与互补在线技术的新组合,这些技术最近在 X 射线和中子的大科学设施上得以实现。这项新兴技术能够进行同步多方法研究,为同时表征 LNPs 的结构以及化学或机械性能提供了令人兴奋的机会。
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