Unraveling the cell-type dependent radiosensitizing effects of gold through the development of a multifunctional gold nanoparticle
Open accessAbstract
The radiosensitizing efficacy of gold is well established, however, there remain several significant barriers to the successful clinical translation of nano-sized gold particles (AuNPs). These barriers include: retaining stability in relevant biological sera, demonstrating effectiveness at clinically relevant AuNP concentrations and identifying the biological context where significant benefit is most likely to be achieved. Herein we have developed a AuNP preparation, stress-tested to provide effective protection from salt and serum mediated agglomeration. Furthermore, the core AuNP is co-functionalized with two biologically derived peptides designed to enhance endocytosis and promote endosomal escape, thus maximizing intracellular AuNP surface area. In summary, these investigations demonstrate restored AuNP internalization using the co-functionalized preparation that generated significant radiosensitization, in both in vitro and in vivo models, at clinically viable treatment concentrations. Furthermore, we have identified an underpinning biological mechanism in the inherent radical scavenging capacity that could be used to predict radiosensitizing efficacy.
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Gold-based nanoparticles were the most frequently investigated class, followed by silver-, platinum-, bismuth-, and gadolinium-based platforms.
“Gold-based nanoparticles were the most frequently investigated class [20,24,27,28,29], followed by silver-, platinum-, bismuth-, and gadolinium-based platforms [15,30,31,32,33,34,35,36].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [28]
The Introduction (page unavailable) describes prior studies of gold nanoparticles, and the Discussion (page unavailable) reports this paper’s investigation of a gold nanoparticle. Neither passage compares how frequently gold platforms were investigated with other nanoparticle classes, so the 'most frequently investigated' ranking is unsupported. The citation is attached to the gold clause, not the subsequent list of other metals. (LLM, conf=0.82)
Experimental — accuracy not yet measuredHigh-Z nanoplatforms based on silver, gadolinium, platinum, gold, and bismuth enhance radiation-induced energy deposition through photoelectric interactions and secondary electron generation.
“High-atomic-number (high-Z) nanoplatforms based on silver (Z = 47), gadolinium (Z = 64), platinum (Z = 78), gold (Z = 79), and bismuth (Z = 83) enhance radiation-induced energy deposition through photoelectric interactions and secondary electron generation [15,20,27,28,30,33,34,36,50,63].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [28]
The Introduction describes gold nanoparticles as radiosensitisers and links the effect partly to gold’s high mass absorption coefficient. The Discussion describes secondary-electron deposition after gold nanoparticle ionisation, but the paper does not establish the claimed mechanism for silver, gadolinium, platinum, or bismuth, nor does it explicitly identify photoelectric interactions. (LLM, conf=0.88)
Experimental — accuracy not yet measuredHigh-atomic-number nanomaterials were reported to increase local radiation energy deposition through photoelectric interactions, resulting in secondary electrons and localized dose amplification.
“High-atomic-number (high-Z) nanomaterials were reported to increase local radiation energy deposition through photoelectric interactions, resulting in the generation of secondary electrons and localized dose amplification [15,20,27,28,34].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [28]
The Introduction (page unavailable) attributes gold nanoparticle radiosensitization partly to gold’s high mass absorption coefficient. The Discussion (page unavailable) describes secondary-electron deposition after gold nanoparticle ionization and high doses deposited within about 10 nm. The copy does not specify photoelectric interactions or establish the mechanism for high-Z nanomaterials generally. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe earliest and most extensively investigated approach is conventional radiotherapy enhancement based on high-atomic-number nanomaterials, including gold, silver, platinum, bismuth, gadolinium, and hafnium-containing nanoparticles.
“The earliest and most extensively investigated approach is conventional radiotherapy enhancement based on high-atomic-number (high-Z) nanomaterials, including gold, silver, platinum, bismuth, gadolinium, and hafnium-containing nanoparticles [15,20,27,28,30,33,34,36,50,63].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [28]
The Introduction (page unavailable) describes gold nanoparticles as proven radiosensitisers and discusses the substantial research on them. The paper does not establish that high-Z nanomaterial enhancement was the earliest or most extensively investigated approach, or address the other listed metals as radiosensitisers. (LLM, conf=0.86)
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Hullo, M., Grall, R., Perrot, Y., Mathé, C., Ménard, V., Yang, X., Lacombe, S., Porcel, E., Villagrasa, C., Chevillard, S., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094436 · Cited by 48 · see citing works
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“High-atomic-number (high-Z) nanomaterials were reported to increase local radiation energy deposition through photoelectric interactions, resulting in the generation of secondary electrons and localized dose amplification [15,20,27,28,34].”
Influential
- Authors
- Nicol, J. R., Harrison, E., O'Neill, S. M., Dixon, D., McCarthy, H. O., & Coulter, J. A.
- Affiliations
- Queen's University Belfast (GB)
- University of Ulster (GB)
- Corresponding author
- Coulter, Jonathan A.
- Venue
- Nanomedicine: Nanotechnology, Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 14
- Issue
- 2
- Pages
- 439-449
- ISSN
- 1549-9634 (ISSN-L)
- OpenAlex
- W2772312061
- Cited by
- 18
- References
- 51
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 3
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nanomedicine Nanotechnology Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Ulster University Research Portal (Ulster University) (publishedVersion, cc-by-nc-nd)
- Research Portal (Queen's University Belfast) (submittedVersion, cc-by-nc-nd)
- Funders
- EPSRC (EP/K039342/1)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Physical Sciences › Materials Science › Electronic, Optical and Magnetic Materials › Gold and Silver Nanoparticles Synthesis and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- gold nanoparticles, radiosensitization, nanoparticle agglomeration, serum stability, peptide functionalization, endocytosis, endosomal escape, free radical scavenging, clinical translation
- MeSH terms
- Animals, Breast Neoplasms, DNA Damage, Endocytosis, Female, Gold, Humans, Mice, Inbred BALB C, Peptide Fragments, Radiation-Sensitizing Agents, Tumor Cells, Cultured, Mice, SCID, Reactive Oxygen Species, Xenograft Model Antitumor Assays, Cell Proliferation, Metal Nanoparticles
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