Gold Nanoparticle Size, Biodistribution, and Toxicity: Insights from DualEnergy CT

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Year : 2026 | Volume : 28 | 02 | Page :
    By

    Atul Khajuria,

  • Kiran Kumari,

  • Tapaswi Ram Khajuria,

  1. Faculty, Department of Allied & Health Care Sciences, Desh Bhagat University, Off NH-44, Amloh Road, Mandi Gobindgarh, District Fatehgarh Sahib, punjab, india
  2. Retd. Govt. Master, Department of Education, Govt. High School, Pachote, Chenani, Udhampur, jammu & kashmir, India
  3. Retd. Lecturer, Department of Education, Govt. Higher Sec School, Barola, Udhampur, jammu & kashmir, India

Abstract

Dual-energy and spectral computed tomography (CT) have emerged as powerful platforms for noninvasive, quantitative mapping of nanoparticle biodistribution in vivo. By exploiting the energy-dependent attenuation profiles of high-atomic-number (high-Z) materials, these systems enable material decomposition and element-specific imaging, thereby distinguishing nanoparticle signals from those of soft tissues and conventional iodinated contrast agents. Photon-counting spectral CT further enhances this capability by binning individual photons into multiple energy channels, improving spatial resolution, contrast-to-noise ratio, and enabling K-edge imaging for precise elemental identification. Among available nano-contrast agents, gold nanoparticles (AuNPs) have attracted particular attention due to their high atomic number (Z = 79), excellent X-ray attenuation, tunable size, and versatile surface chemistry. These properties make AuNPs highly suitable for vascular imaging, tumor targeting, and molecular CT applications. Studies have demonstrated that AuNPs provide prolonged vascular enhancement compared with iodine-based agents, with circulation times modifiable through surface coatings such as polyethylene glycol (PEG). Functionalization with targeting ligands—including peptides, antibodies, and folate—enables receptor-specific accumulation in tumors and inflamed tissues, enhancing lesion detectability and diagnostic accuracy. A critical determinant of AuNP performance is particle size, which directly influences pharmacokinetics, biodistribution, and clearance pathways. Smaller nanoparticles (approximately 5–20 nm) exhibit prolonged circulation, reduced uptake by the reticuloendothelial system (RES), and more uniform tissue distribution. In contrast, larger particles tend to accumulate rapidly in the liver and spleen due to macrophage-mediated clearance. Surface charge and coating further modulate protein adsorption, immune recognition, and biological interactions, thereby affecting imaging outcomes and quantification accuracy. Quantitative assessment of biodistribution using dual-energy CT relies on calibration with phantoms containing known nanoparticle concentrations, followed by acquisition under standardized imaging conditions and application of material decomposition algorithms. Strong correlations between CT-derived concentrations and ex vivo analytical techniques, such as inductively coupled plasma mass spectrometry, validate the reliability of spectral CT for nanoparticle tracking. Despite these advances, concerns regarding long-term retention, potential toxicity, and regulatory challenges persist. Accumulation in RES organs raises questions about chronic exposure, while variations in nanoparticle synthesis and functionalization complicate standardization. Nevertheless, ongoing improvements in CT hardware, including photon- counting detectors, and advances in nanoparticle engineering continue to expand the clinical potential of AuNP-based imaging. This integration of nanotechnology with advanced imaging modalities represents a promising frontier for precision diagnostics, enabling simultaneous visualization, quantification, and targeting of disease processes at the molecular level.

Keywords: Gold nanoparticles, Dual-energy CT, Spectral CT, Photon-counting CT, Biodistribution, Nanoparticle size, Toxicity, Molecular imaging.

How to cite this article:
Atul Khajuria, Kiran Kumari, Tapaswi Ram Khajuria. Gold Nanoparticle Size, Biodistribution, and Toxicity: Insights from DualEnergy CT. Nano Trends – A Journal of Nano Technology & Its Applications. 2026; 28(02):-.
How to cite this URL:
Atul Khajuria, Kiran Kumari, Tapaswi Ram Khajuria. Gold Nanoparticle Size, Biodistribution, and Toxicity: Insights from DualEnergy CT. Nano Trends – A Journal of Nano Technology & Its Applications. 2026; 28(02):-. Available from: https://journals.stmjournals.com/nts/article=2026/view=244504


References

  1. Hainfeld Joshua F, Slatkin Daniel N, Focella Thomas M, Smilowitz Henry M. Gold nanoparticles: a new X-ray contrast agent. Br J Radiol. 2006;79(939):248-253.
  2. Johnson Thomas R. Dual-energy CT: general principles. AJR Am J Roentgenol. 2012;199(5 Suppl): S3-S8.
  3. Roessl Ewald, Proksa Roland. K-edge imaging in X-ray computed tomography using multi-bin photon counting detectors. Phys Med Biol. 2007;52(15):4679-4696.
  4. Popovtzer Ron, Agrawal Amit, Kotov Nicholas A, Popovtzer Aron, Balter James, Carey Thomas E. Targeted gold nanoparticles enable molecular CT imaging of
    cancer. Nano Lett. 2008;8(12):4593-4599.
  5. Cormode David P, Roessl E, Thran A, Skajaa T, Gordon Robert E, Schlomka Joerg P. Atherosclerotic plaque composition analysis with multicolor CT. Radiology.
    2010;256(3):774-782.
  6. Hyafil Fabien, Cornily Jean-Christophe, Feig Jonathan E., Gordon Ronald, Vucic Emilie, Amirbekian Vasken. Noninvasive detection of macrophages using
    nanoparticulate CT agent. Nat Med. 2007;13(5):636-641.
  7. Pan D, Lanza Gregory M, Wickline Samuel A, Caruthers Samuel D. Nanomedicine: ligand-directed molecular imaging. Eur J Radiol. 2009;70(2):274-285.
  8. Chen Yan, Xianyu Yulei, Jiang Xiaoyuan. Size-dependent toxicity of gold nanoparticles. Biochem Biophys Res Commun. 2016;478(3):1206-1212.
  9. Khlebtsov Nikolai, Dykman Lev. Biodistribution and toxicity of engineered gold nanoparticles: review. Chem Soc Rev. 2011;40(3):1647-1671.
  10. Albanese Andrew, Tang Peter S, Chan Warren C W. The effect of nanoparticle size on biological systems. Annu Rev Biomed Eng. 2012;14:1-16.
  11. Perrault Scott D, Walkey Carl, Jennings Thomas, Fischer Hans C, Chan Warren C W. Mediating tumor targeting efficiency of nanoparticles through design. Nano Lett. 2009;9(5):1909-1915.
  12. Choi Hye Jin, Liu Wenjun, Misra Pradeep, Tanaka Eiji, Zimmer Jason P, Ipe Bianca I. Renal clearance of quantum dots. Nat Biotechnol. 2007;25(10):1165-1170.
  13. Longmire Michelle, Choyke Peter L, Kobayashi Hisataka. Clearance properties of nano-sized particles and molecules as imaging agents. Nanomedicine. 2008;3(5):703-717.
  14. Jokerst Jesse V, Lobovkina Tatiana, Zare Richard N, Gambhir Sanjiv S. Nanoparticle PEGylation for imaging and therapy. Nanomedicine (Lond). 2011;6(4):715-728.
  15. Liu Yuling, Ai Kelvin, Lu Lin. Polydopamine and its derivative materials: synthesis and biomedical applications. Chem Rev. 2014;114(9):5057-5115.
  16. Kim Dong-Hyun, Nikles David E, Brazel Christopher S, DeSimone Joseph M. Polymer-coated nanoparticles for imaging and therapy. Adv Drug Deliv Rev. 2009;61(6):457-466.
  17. Decuzzi Paolo, Ferrari Mauro. The receptor-mediated endocytosis of nonspherical particles. Biophys J. 2008;94(10):3790-3797.
  18. Albanese Andrew, Chan Warren C W. Effect of gold nanoparticle aggregation on cell uptake and toxicity. ACS Nano. 2011;5(7):5478-5489.
  19. Park Ji-Ho, Gu Lanyuan, von Maltzahn Georg, Ruoslahti Erkki, Bhatia Sangeeta N, Sailor Michael J. Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nat Mater. 2009;8(4):331-336.
  20. Chithrani B Devika, Ghazani A Arash, Chan Warren C W. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett.
    2006;6(4):662-668.
Ahead of Print Subscription Review Article
Volume 28
02
Received 12/02/2026
Accepted 25/04/2026
Published 20/05/2026
Publication Time 97 Days
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