Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, 37235, USA.
Nanovaccine Institute, Iowa State University, Ames, IA, 50012, USA.
Small. 2023 Jul;19(29):e2204293. doi: 10.1002/smll.202204293. Epub 2023 Mar 25.
The in vivo dynamics of nanoparticles requires a mechanistic understanding of multiple factors. Here, for the first time, the surprising breakdown of functionalized gold nanostars (F-AuNSs) conjugated with antibodies and Cu radiolabels in vivo and in artificial lysosomal fluid ex vivo, is shown. The short-term biodistribution of F-AuNSs is driven by the route of systemic delivery (intravenous vs intraperitoneal) and long-term fate is controlled by the tissue type in vivo. In vitro studies including endocytosis pathways, intracellular trafficking, and opsonization, are combined with in vivo studies integrating a milieu of spectroscopy and microcopy techniques that show F-AuNSs dynamics is driven by their physicochemical properties and route of delivery. F-AuNSs break down into sub-20 nm broken nanoparticles as early as 7 days postinjection. Martini coarse-grained simulations are performed to support the in vivo findings. Simulations suggest that shape, size, and charge of the broken nanoparticles, and composition of the lipid membrane depicting various tissues govern the interaction of the nanoparticles with the membrane, and the rate of translocation across the membrane to ultimately enable tissue clearance. The fundamental study addresses critical gaps in the knowledge regarding the fate of nanoparticles in vivo that remain a bottleneck in their clinical translation.
纳米粒子的体内动力学需要对多种因素进行机制理解。在这里，首次展示了与抗体和 Cu 放射性标记物缀合的功能化金纳米星（F-AuNSs）在体内和人工溶酶体液中外体中的功能惊人地破坏。F-AuNSs 的短期生物分布由系统给药途径（静脉内与腹腔内）驱动，而长期命运由体内组织类型控制。包括内吞途径、细胞内转运和调理作用在内的体外研究，与整合光谱和显微镜技术的体内研究相结合，表明 F-AuNSs 的动力学是由其物理化学性质和给药途径驱动的。早在注射后 7 天，F-AuNSs 就会分解成小于 20nm 的破碎纳米颗粒。进行了 Martini 粗粒化模拟以支持体内发现。模拟表明，破碎纳米颗粒的形状、大小和电荷以及描绘各种组织的脂质膜的组成决定了纳米颗粒与膜的相互作用以及跨膜转运的速率，从而最终实现组织清除。这项基础研究解决了有关纳米粒子在体内命运的知识中的关键空白，这仍然是其临床转化的瓶颈。
