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Physicochemical Properties and Route of Systemic Delivery Control the In Vivo Dynamics and Breakdown of Radiolabeled Gold Nanostars. | LitMetric

AI Article Synopsis

  • The study explores how functionalized gold nanostars (F-AuNSs), used for medical applications, break down in living organisms and in laboratory conditions, revealing important insights about their behavior over time.
  • It highlights that the way F-AuNSs are delivered (like through injection) affects their short-term distribution, while the type of tissue impacts their long-term fate.
  • Advanced simulations support the findings, showing that factors like shape, size, and charge of the nanoparticles influence their interaction with cellular membranes, which is crucial for understanding how they clear from the body and their potential use in clinical settings.

Article 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 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518372PMC
http://dx.doi.org/10.1002/smll.202204293DOI Listing

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