纳米颗粒的体内动力学需要对多种因素的机械理解。这里,第一次,在体内和离体人工溶酶体液中,与抗体和64个Cu放射性标记缀合的功能化金纳米星(F-AuNS)的惊人分解,显示。F-AuNS的短期生物分布由全身递送途径(静脉内与腹膜内)驱动,并且长期命运由体内组织类型控制。体外研究,包括内吞途径,细胞内贩运,和调理,与体内研究相结合,整合了光谱学和显微技术的环境,这些技术表明F-AuNS动力学是由其理化性质和递送途径驱动的。F-AuNS早在注射后7天就分解成亚20nm破碎的纳米颗粒。进行Martini粗粒模拟以支持体内发现。模拟表明这种形状,尺寸,和破碎的纳米粒子的电荷,和描述各种组织的脂质膜的组成控制纳米颗粒与膜的相互作用,以及最终能够清除组织的跨膜易位率。基础研究解决了关于纳米颗粒在体内命运的知识中的关键差距,这仍然是其临床翻译的瓶颈。
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 64 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.