Physicochemical Properties and Route of Systemic Delivery Control the In Vivo Dynamics and Breakdown of Radiolabeled Gold Nanostars
Date
2023-03-25
Authors
Wen, Xiaona
Ou, Luping
Cutshaw, Gabriel
Uthaman, Saji
Ou, Yu-Chuan
Zhu, Tian
Szakas, Sarah
Carney, Brandon
Houghton, Jacob
Gundlach-Graham, Alexander
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Wiley-VCH GmbH
Abstract
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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article
Comments
This is the published version of the following article: Wen, Xiaona, Luping Ou, Gabriel Cutshaw, Saji Uthaman, Yu‐Chuan Ou, Tian Zhu, Sarah Szakas et al. "Physicochemical Properties and Route of Systemic Delivery Control the In Vivo Dynamics and Breakdown of Radiolabeled Gold Nanostars." Small (2023): 2204293.
DOI: 10.1002/smll.202204293.
Copyright 2023 The Authors.
Attribution 4.0 International (CC BY 4.0).
Posted with permission.