Physicochemical Properties and Route of Systemic Delivery Control the In Vivo Dynamics and Breakdown of Radiolabeled Gold Nanostars.
Physicochemical Properties and Route of Systemic Delivery Control the In Vivo Dynamics and Breakdown of Radiolabeled Gold Nanostars.
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DOI：
10.1002/smll.202204293
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发表时间：
2023-07
期刊：
影响因子：
13.3
通讯作者：
Bardhan, Rizia
中科院分区：
文献类型：
--
作者：
Wen, Xiaona;Ou, Luping;Cutshaw, Gabriel;Uthaman, Saji;Ou, Yu-Chuan;Zhu, Tian;Szakas, Sarah;Carney, Brandon;Houghton, Jacob;Gundlach-Graham, Alexander;Rafat, Marjan;Yang, Kai;Bardhan, Rizia
关键词：
纳米颗粒的体内动力学需要从机理上理解多种因素。在这里，第一次展示了功能化的金纳米星(F-AuNSS)在体内和体外人工溶酶体液中与抗体和64Cu放射性标记结合的惊人分解。F-AuNSs的短期生物分布由全身给药途径(静脉给药与腹膜内给药)驱动，长期命运由体内组织类型控制。包括内吞作用、细胞内转运和调理作用在内的体外研究与体内研究相结合，整合了一系列光谱和显微技术，表明F-AuNSs的动力学由它们的物理化学性质和传递途径驱动。F-AuNSS最早在注射后7天就分解成亚20 nm的破碎纳米颗粒。马提尼的粗粒度模拟被用来支持体内的研究结果。模拟表明，破碎的纳米颗粒的形状、大小和电荷，以及描绘各种组织的脂膜的组成，控制着纳米颗粒与膜的相互作用，以及跨膜的转移率，最终使组织得以清除。这项基础性研究解决了有关纳米粒子在体内的命运的知识中的关键空白，这些知识仍然是它们临床翻译的瓶颈。
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 64Cu 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.
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