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.
Original language | English |
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Article number | 2204293 |
Journal | Small |
Volume | 19 |
Issue number | 29 |
DOIs | |
State | Published - Jul 19 2023 |
Externally published | Yes |
Funding
The authors gratefully acknowledge Dr. Evan Krystofiak's assistance with TEM imaging in vivo, and identification of cellular structures in tissues in TEM. X.W. acknowledges support from the CDMRP Career grant W81XWH1810139. Y.O. was supported through NSF grant CMMI‐1634856. L.O. and K.Y. thank the support of the open research fund from Songshan Lake Materials Laboratory 2021SLABFK10 and the National Natural Science Foundation of China 21774092. T.Z. and M.R. acknowledge support from NIH R00CA201304. G.C., S.U., and R.B. acknowledge support from the CDMRP Career grant W81XWH1810139 and NIH grant 1R01EB029756‐01A1. The authors gratefully acknowledge Dr. Evan Krystofiak's assistance with TEM imaging in vivo, and identification of cellular structures in tissues in TEM. X.W. acknowledges support from the CDMRP Career grant W81XWH1810139. Y.O. was supported through NSF grant CMMI-1634856. L.O. and K.Y. thank the support of the open research fund from Songshan Lake Materials Laboratory 2021SLABFK10 and the National Natural Science Foundation of China 21774092. T.Z. and M.R. acknowledge support from NIH R00CA201304. G.C., S.U., and R.B. acknowledge support from the CDMRP Career grant W81XWH1810139 and NIH grant 1R01EB029756-01A1. Open access funding provided by the Iowa State University Library.
Keywords
- Martini coarse-grained simulations
- exocytosis
- gold nanostars
- in vivo breakdown
- long-term biodistribution
- positron emission tomography (PET)
- protein corona