Gold nanoparticle enhancement of stereotactic radiosurgery for neovascular age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries for people over the age of 50. In this work, the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance kilovoltage stereotactic radiosurgery for neovascular AMD is investigated. Microdosimetry calculations at the sub-cellular level were carried out to estimate the radiation dose enhancement to individual nuclei in neovascular AMD endothelial cells (nDEF) due to photon-induced photo-/Auger electrons from x-ray-irradiated AuNP. The nDEF represents the ratio of radiation doses to the endothelial cell nuclei with and without AuNP. The calculations were carried out for a range of feasible AuNP local concentrations using the clinically applicable 100 kVp x-ray beam parameters employed by a commercially available x-ray therapy system. The results revealed nDEF values of 1.30-3.26 for the investigated concentration range of 1-7 mg g(-1), respectively. In comparison, for the same concentration range, nDEF values of 1.32-3.40, 1.31-3.33, 1.29-3.19, 1.28-3.12 were calculated for 80, 90, 110 and 120 kVp x-rays, respectively. Meanwhile, calculations as a function of distance from the AuNP showed that the dose enhancement, for 100 kVp, is markedly confined to the targeted neovascular AMD endothelial cells where AuNP are localized. These findings provide impetus for considering the application of AuNP to enhance therapeutic efficacy during stereotactic radiosurgery for neovascular AMD.

Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation

“…The results of this MC simulation provide further confirmation of the potential to increase DER with AuNP from previous analytical calculations (Ngwa et al 2012a). The clinical feasibility of AuNP targeting of macular endothelial cells via direct injection or via periocular routes must be addressed in experimental studies since the AuNP location is critical to obtain the desired dose enhancement.…”

Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation

“…The results of this MC simulation provide further confirmation of the potential to increase DER with AuNP from previous analytical calculations (Ngwa et al 2012a). The clinical feasibility of AuNP targeting of macular endothelial cells via direct injection or via periocular routes must be addressed in experimental studies since the AuNP location is critical to obtain the desired dose enhancement.…”

Gold nanoparticles in ophthalmology

“…The previous analytical calculations of Ngwa et al. led to the same conclusion . The GNP in AMD therapy could be useful for both their antiangiogenic properties and their ability to improve the therapy by stereotactic radiosurgery.…”

Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization

“…Targeting RT to tumor-associated endothelial cells with GNPs can break this tumor-protective cycle–damaged endothelial cells and vasculature will fail to deliver nutrients to tumor tissue, leading to ischemic necrosis and reduced VEGF production. Ngwa et al have proposed that GNPs can serve as tumor “vascular dose-painting” (VDP) agents [49], [58]–GNPs actively circulating through the abnormal and tortuous tumor blood vessels can locally enhance the dose of radiation absorbed by endothelial cells lining the vascular walls. Such endothelial cell damage may also facilitate the loosening of tight junctions in the BBB with lower radiation doses.…”

Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation

“…The results of this MC simulation provide further confirmation of the potential to increase DER with AuNP from previous analytical calculations (Ngwa et al 2012a). The clinical feasibility of AuNP targeting of macular endothelial cells via direct injection or via periocular routes must be addressed in experimental studies since the AuNP location is critical to obtain the desired dose enhancement.…”

Gold nanoparticles in ophthalmology

“…The previous analytical calculations of Ngwa et al. led to the same conclusion . The GNP in AMD therapy could be useful for both their antiangiogenic properties and their ability to improve the therapy by stereotactic radiosurgery.…”

Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization

“…Targeting RT to tumor-associated endothelial cells with GNPs can break this tumor-protective cycle–damaged endothelial cells and vasculature will fail to deliver nutrients to tumor tissue, leading to ischemic necrosis and reduced VEGF production. Ngwa et al have proposed that GNPs can serve as tumor “vascular dose-painting” (VDP) agents [49], [58]–GNPs actively circulating through the abnormal and tortuous tumor blood vessels can locally enhance the dose of radiation absorbed by endothelial cells lining the vascular walls. Such endothelial cell damage may also facilitate the loosening of tight junctions in the BBB with lower radiation doses.…”

Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation

“…The results of this MC simulation provide further confirmation of the potential to increase DER with AuNP from previous analytical calculations (Ngwa et al 2012a). The clinical feasibility of AuNP targeting of macular endothelial cells via direct injection or via periocular routes must be addressed in experimental studies since the AuNP location is critical to obtain the desired dose enhancement.…”

Gold nanoparticles in ophthalmology

“…The previous analytical calculations of Ngwa et al. led to the same conclusion . The GNP in AMD therapy could be useful for both their antiangiogenic properties and their ability to improve the therapy by stereotactic radiosurgery.…”

Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization

“…Targeting RT to tumor-associated endothelial cells with GNPs can break this tumor-protective cycle–damaged endothelial cells and vasculature will fail to deliver nutrients to tumor tissue, leading to ischemic necrosis and reduced VEGF production. Ngwa et al have proposed that GNPs can serve as tumor “vascular dose-painting” (VDP) agents [49], [58]–GNPs actively circulating through the abnormal and tortuous tumor blood vessels can locally enhance the dose of radiation absorbed by endothelial cells lining the vascular walls. Such endothelial cell damage may also facilitate the loosening of tight junctions in the BBB with lower radiation doses.…”