Academic Journal
Gold Nanoparticle Radiosensitization for High-Dose-Rate Brachytherapy: Differential Efficacy of PEG- and RGD-Functionalized Gold Nanoparticles Across 2-Dimensional, 3-Dimensional, and in vivo Prostate Cancer Models.
| Title: | Gold Nanoparticle Radiosensitization for High-Dose-Rate Brachytherapy: Differential Efficacy of PEG- and RGD-Functionalized Gold Nanoparticles Across 2-Dimensional, 3-Dimensional, and in vivo Prostate Cancer Models. |
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| Authors: | Cecchi D; Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada., Jackson N; Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada., Karaman D; Department of Mechanical Engineering, University of Victoria, Victoria, BC, Canada.; Axolotl Biosciences, Victoria, BC, Canada., Beckham W; Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada., Johnstone CD; Medical Physics Department, BC Cancer, Vancouver, BC, Canada., Lloyd SAM; Medical Physics Department, BC Cancer, Vancouver, BC, Canada.; Division of Radiation Oncology, University of British Columbia, Vancouver, BC, Canada., Chithrani D; Department of Physics and Astronomy, University of Victoria, Victoria, BC, Canada.; Medical Physics Department, BC Cancer, Victoria, BC, Canada.; Centre for Advanced Materials and Related Technologies (CAMTEC), University of Victoria, Victoria, BC, Canada. |
| Source: | International journal of nanomedicine [Int J Nanomedicine] 2026 Jun 12; Vol. 21, pp. 599472. Date of Electronic Publication: 2026 Jun 12 (Print Publication: 2026). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: DOVE Medical Press Country of Publication: New Zealand NLM ID: 101263847 Publication Model: eCollection Cited Medium: Internet ISSN: 1178-2013 (Electronic) Linking ISSN: 11769114 NLM ISO Abbreviation: Int J Nanomedicine Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Auckland : DOVE Medical Press |
| MeSH Terms: | Metal Nanoparticles*/administration & dosage , Metal Nanoparticles*/chemistry , Radiation-Sensitizing Agents*/chemistry , Radiation-Sensitizing Agents*/pharmacokinetics , Radiation-Sensitizing Agents*/pharmacology , Prostatic Neoplasms*/pathology , Prostatic Neoplasms*/radiotherapy, Nanoparticles/chemistry ; Gold/chemistry ; Polyethylene Glycols/chemistry ; Oligopeptides/chemistry ; Oligopeptides/pharmacology ; Cell Survival/drug effects ; Cell Survival/radiation effects ; Brachytherapy/methods ; Humans ; Male ; Middle Aged ; Aged ; Aged, 80 and over ; Animals ; Mice |
| Abstract: | Purpose: Gold nanoparticles (GNPs) are promising radiosensitizing agents for radiation therapy; however, their implementation into high dose rate brachytherapy (HDR-BT) remains underexplored. Surface functionalization with polyethylene glycol (PEG) or integrin-binding domain RGD impacts their biodistribution and intracellular uptake, but whether active cellular targeting via RGD improves radiosensitization for HDR-BT has not been established in vivo. Methods: Here, we systematically compare the radiosensitization efficacy of non-targeted PEGylated GNPs versus actively targeted PEG-RGD GNPs on PC3 prostate cancer cells in vitro and in vivo, using clinically plausible concentrations, dosing procedures, and purpose-built irradiation platforms. 2-dimensional (2-D) and 3-dimensional (3-D) cell cultures, and male NRG mice were irradiated via a 192-Ir source delivered from a clinical HDR-BT afterloader. In vitro samples were dosed at 10 μg [Au]/mL and mice were intratumourally injected with 50 μL at 2 mg [Au]/kg bodyweight. Results: PEGylated GNPs did not elicit any radiosensitization either in 2-D, 3-D, or in vivo. RGD-functionalized GNPs elicited a 17% (p=0.001) reduction in survival fraction and 33% (p=0.005) greater DNA DSBs in 2-D cell cultures, and 57% (p<0.0001) reduction in 3-D spheroid growth compared to control samples 14 days post-irradiation. In a pre-clinical mouse xenograft model, tumour volume growth was also significantly reduced by 28% (p=0.005) 20 days post-irradiation compared to the irradiated control group, with no observable signs of acute toxicity from radiation delivery or administered GNPs. Conclusion: This research represents the first systematic in vitro and in vivo demonstration of GNP-induced radiosensitization using an HDR-BT source with clinically informed intratumoural delivery. Active cellular targeting with RGD functionalization was found to be a critical determinant of radiosensitization efficacy both in vitro and in vivo. Both GNP formulations demonstrated tolerability at the delivered dosing concentrations, and further research into the clinical deliverability of GNPs for HDR-BT is necessitated. (© 2026 Cecchi et al.) |
| Competing Interests: | The authors have no competing interests to report. |
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| Contributed Indexing: | Keywords: gold nanoparticles; high dose rate brachytherapy; radiosensitization; radiotherapy |
| Substance Nomenclature: | 7440-57-5 (Gold) 3WJQ0SDW1A (Polyethylene Glycols) 0 (Radiation-Sensitizing Agents) 0 (Oligopeptides) 78VO7F77PN (arginyl-glycyl-aspartic acid) |
| Entry Date(s): | Date Created: 20260618 Date Completed: 20260626 Latest Revision: 20260813 |
| Update Code: | 20260813 |
| PubMed Central ID: | PMC13271069 |
| DOI: | 10.2147/IJN.S599472 |
| PMID: | 42311423 |
| Database: | MEDLINE |
| ISSN: | 1178-2013 |
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| DOI: | 10.2147/IJN.S599472 |