Physicochemical Properties and Route of Systemic Delivery Control the In Vivo Dynamics and Breakdown of Radiolabeled Gold Nanostars
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 25, 2023
- Source ID
- 10.1002/smll.202204293
Entities
People
- Alexander Gundlach‐graham
- Brandon Carney
- Gabriel Cutshaw
- Jacob Houghton
- Kai Yang
- Luping Ou
- Marjan Rafat
- Rizia Bardhan
- Saji Uthaman
- Sarah Szakas
- Tian Zhu
- Xiaona Wen
- Yu‐chuan Ou
Organizations
- Congressionally Directed Medical Research Programs
- Iowa State University
- National Institutes of Health
- National Natural Science Foundation of China
- National Science Foundation
- Soochow University
- Stony Brook University
- Vanderbilt University