Volume 5 Number 1 2026
Long-Term Biodistribution, Biotransformation, and Safety of Fe3O4@Au Hybrid Nanoparticles: Implications for Clinical Translation in Theranostic Nanomedicine
Rajesh Thangarajan 1*, Gnanasekaran Ashok 2
Biosensors and Nanotheranostics 5 (1) 1-8 https://doi.org/10.25163/biosensors.5110992
Submitted: 25 March 2026 Revised: 11 May 2026 Accepted: 21 May 2026 Published: 23 May 2026
Hybrid nanostructures that fuse a magnetic iron oxide core with gold have become one of the more compelling ideas in precision nanomedicine, because a single particle can, in principle, both report on disease and treat it. Yet the question that matters most for patients is not what these particles do in the first hours after injection but where they go, what they turn into, and whether they leave. This review synthesizes recent preclinical evidence, anchored by a 12-month in vivo study of laser-ablated Fe3O4@Au core–satellite nanoparticles, to trace that long arc. After intravenous dosing, PEGylated hybrids circulate for a few hours, acquire a protein corona, and are then captured largely by Kupffer cells and splenic macrophages, which sequester the bulk of the injected dose within a day. Because intact constructs far exceed the ~5.5–8 nm renal threshold, elimination falls to the slow hepatobiliary route rather than the kidneys. Over months, the two metals diverge: the iron oxide core dissolves in the acidic phagolysosome and its liberated iron is folded into ferritin and hemosiderin, while the inert gold satellites resist degradation and slowly aggregate in situ. Longitudinal CT and MRI capture this divergence as a gradual fall in gold signal alongside a recovery of hepatic T2 contrast between 6 and 12 months. Reassuringly, high-dose animals survived to 365 days with normal weight gain, unremarkable liver and kidney biochemistry, and no fibrosis or necrosis on histology. Taken together, the evidence supports cautious optimism while underscoring that persistent gold storage remains the central design problem for clinical translation.
Keywords: gold–iron oxide hybrid nanoparticles; Fe3O4@Au core–satellite nanostructures; theranostic nanomedicine; long-term biodistribution; hepatobiliary excretion; mononuclear phagocyte system; Kupffer cells; protein corona; iron oxide biodegradation; gold nanoparticle persistence; in vivo toxicity; CT/MRI imaging
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