Targeted nanoparticles for tumour radiotherapy enhancement-the long dawn of a golden era? (original) (raw)
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Nanoscale, 2016
A major problem in the treatment of head and neck cancer today is the resistance of tumors to traditional radiation therapy, which results in 40% local failure, despite aggressive treatment. The main objective of this study was to develop a technique which will overcome tumor radioresistance by increasing the radiation absorbed in the tumor using cetuximab targeted gold nanoparticles (GNPs), in clinically relevant energies and radiation dosage. In addition, we have investigated the biological mechanisms underlying tumor shrinkage and the in vivo toxicity of GNP. The results showed that targeted GNP enhanced the radiation effect and had a significant impact on tumor growth (P < 0.001). The mechanism of radiation enhancement was found to be related to earlier and greater apoptosis (TUNEL assay), angiogenesis inhibition (by CD34 level) and diminished repair mechanism (PCNA staining). Additionally, GNPs have been proven to be safe as no evidence of toxicity has been observed.
Abstract 2679: Gold nanoparticles enhance the radiation therapy of a murine squamous cell carcinoma
Cancer Research, 2011
The purpose of this study is to test the hypothesis that gold nanoparticle (AuNp, nanogold)-enhanced radiation therapy (nanogold radiation therapy, NRT) is efficacious when treating the radiation resistant and highly aggressive mouse head and neck squamous cell carcinoma model, SCCVII, and to identify parameters influencing the efficacy of NRT. Subcutaneous (sc) SCCVII leg tumors in mice were irradiated with x-rays at the Brookhaven National Laboratory (BNL) National Synchrotron Light Source (NSLS) with and without prior intravenous (iv) administration of AuNPs. Variables studied included radiation dose, beam energy, temporal fractionation and hyperthermia. AuNPmediated NRT was shown to be effective for the sc SCCVII model. AuNPs were more effective aI 42 Gy than at 30 Gy (both at 68 kev median beam energy) compared to controls without gold. Similarly, at 157 keV median beam energy, 50.6 Gy NRT was more effective than 44 Gy NRT. At the same radiation dose 1-42 Gy), 68 keV was more effective than 157 keV Hyperthermia and radiation therapy (RT) were synergistic and AuNPs enhanced this synergy, thereby further reducing TCD50 s (tumor control dose 507o) and increasing long-term survivals. It is concluded that gold nanopafticles enhance the radiation therapy of a radioresistant mouse squamous cell carcinoma. The data show that radiation dose, energy and hyperthermia influence efficacy and better define the potential utility of gold nanoparticles for cancer x-ray therapy.
Gold nanoparticles enhance the radiation therapy of a murine squamous cell carcinoma
Physics in Medicine and Biology, 2010
The purpose of this study is to test the hypothesis that gold nanoparticle (AuNP, nanogold)-enhanced radiation therapy (nanogold radiation therapy, NRT) is efficacious when treating the radiation resistant and highly aggressive mouse head and neck squamous cell carcinoma model, SCCVII, and to identify parameters influencing the efficacy of NRT. Subcutaneous (sc) SCCVII leg tumors in mice were irradiated with x-rays at the Brookhaven National Laboratory (BNL) National Synchrotron Light Source (NSLS) with and without prior intravenous (iv) administration of AuNPs. Variables studied included radiation dose, beam energy, temporal fractionation and hyperthermia. AuNPmediated NRT was shown to be effective for the sc SCCVII model. AuNPs were more effective at 42 Gy than at 30 Gy (both at 68 keV median beam energy) compared to controls without gold. Similarly, at 157 keV median beam energy, 50.6 Gy NRT was more effective than 44 Gy NRT. At the same radiation dose (∼42 Gy), 68 keV was more effective than 157 keV. Hyperthermia and radiation therapy (RT) were synergistic and AuNPs enhanced this synergy, thereby further reducing TCD50 s (tumor control dose 50%) and increasing long-term survivals. It is concluded that gold nanoparticles enhance the radiation therapy of a radioresistant mouse squamous cell carcinoma. The data show that radiation dose, energy and hyperthermia influence efficacy and better define the potential utility of gold nanoparticles for cancer x-ray therapy.
Role of Gold Nanoparticles in Enhancing Radiotherapy
Gold nanoparticles have gained significant attention in the field of cancer therapy due to their unique properties and potential to enhance radiotherapy. This review provides an overview of the mechanisms by which gold nanoparticles enhance radiotherapy, including increased radiation absorption, generation of secondary low-energy electrons, dose enhancement effects, and modulation of the tumor microenvironment. The selective targeting and localization of gold nanoparticles in tumor tissues are discussed, highlighting the importance of surface modifications and functionalization. Furthermore, the utilization of gold nanoparticles in imaging techniques and treatment monitoring is explored, emphasizing their optical and photothermal properties. Preclinical studies using in vitro and in vivo models demonstrate the enhanced radiotherapy effects of gold nanoparticles. Th e ongoing clinical trials and translational research are summarized to assess the safety and efficacy of gold nanoparticle-enhanced radiotherapy in human subjects. The potential impact on cancer treatment and patient outcomes is discussed, along with the challenges and future perspectives in optimizing gold nanoparticle properties, standardizing protocols, addressing safety concerns, and integrating with other treatment modalities. In conclusion, gold nanoparticle-enhanced radiotherapy holds great promise in cancer treatment and further research is needed to fully exploit its potential and translate it into clinical practice.
Radiotherapy enhancement with gold nanoparticles
Journal of Pharmacy and Pharmacology, 2008
Gold is an excellent absorber of X-rays. If tumours could be loaded with gold, this would lead to a higher dose to the cancerous tissue compared with the dose received by normal tissue during a radiotherapy treatment. Calculations indicate that this dose enhancement can be significant, even 200% or greater. In this paper, the physical and biological parameters affecting this enhancement are discussed. Gold nanoparticles have shown therapeutic efficacy in animal trials and these results are reviewed. Some 86% long-term (>1 year) cures of EMT-6 mouse mammary subcutaneous tumours was achieved with an intravenous injection of gold nanoparticles before irradiation with 250-kVp photons, whereas only 20% were cured with radiation alone. The clinical potential of this approach is also discussed.
International journal of radiation biology, 2016
Purpose Radiolabeled antibodies and peptides hold promise for molecular radiotherapy but are often limited by a low payload resulting in inadequate delivery of radioactivity to tumour tissue and, therefore, modest therapeutic effect. We developed a facile synthetic method of radiolabeling indium-111 ((111)In) to epidermal growth factor (EGF)-gold nanoparticles ((111)In-EGF-Au NP) with a high payload. Materials and methods EGF-Au NP were prepared via an interaction between gold and the disulphide bonds of EGF and radiolabeled using (111)InCl3. Targeting efficiency was investigated by quantitating internalized radioactivity and by confocal imaging following exposure of MDA-MB-468 (1.3 × 10(6) EGFR/cell) and MCF-7 (10(4) EGFR/cell) cells to Cy3-EGF-Au NP. Cytotoxicity was evaluated in clonogenic assays. Results The proportion of total administered radioactivity that was internalized by MDA-MB-468 and MCF-7 cells was 15% and 1.3%, respectively (mixing ratio of EGF:Au of 160). This diffe...
Investigation of Gold Nanoparticles Effects in Radiation Therapy of Cancer: A Systematic Review
Zanjan University of Medical Sciences, 2022
10.30699/jambs.30.142.388 Background & Objective: In recent years, the use of nanoparticles (NPs), especially gold nanoparticles (GNPs) in radiotherapy, has been repeatedly studied by in-vitro, in-vivo experiments, and Monte Carlo simulation. Some studies declare that specific absorption of GNPs (with a higher atomic number) by cancerous cells increases radiations' lethal effect compared to normal cells. This review article aimed to investigate the radiosensitizing effect of GNPs in cancer radiotherapy. Materials & Methods: Research databases such as Web of Science, PubMed, and Scopus were examined from December 2019. All Gold Nanoparticles Radiation Therapy (GNRT) articles that studied the radiosensitization of gold nanoparticles in radiotherapy were involved in the assessment. Among 706 chosen articles, 52 documents were included in this investigation. Results: The results of all these studies indicate that an increase in tumor mortality happens due to higher radiation absorption by nanoparticles entering the tumor; however, the relationship between the interaction of radiant energy and the size of gold nanoparticles is controversial. Conclusion: This review article will discuss recent advances in the development of gold-based NPs to improve radiotherapy.
The use of gold nanoparticles to enhance radiotherapy in mice
Physics in Medicine and Biology, 2004
Mice bearing subcutaneous EMT-6 mammary carcinomas received a single intravenous injection of 1.9 nm diameter gold particles (up to 2.7 g Au/kg body weight), which elevated concentrations of gold to 7 mg Au/g in tumours. Tumour-to-normal-tissue gold concentration ratios remained ∼8:1 during several minutes of 250 kVp x-ray therapy. One-year survival was 86% versus 20% with x-rays alone and 0% with gold alone. The increase in tumours safely ablated was dependent on the amount of gold injected. The gold nanoparticles were apparently non-toxic to mice and were largely cleared from the body through the kidneys. This novel use of small gold nanoparticles permitted achievement of the high metal content in tumours necessary for significant high-Z radioenhancement.
Gold nanoparticles for cancer radiotherapy: a review
Cancer Nanotechnology, 2016
Background Cancer is one of the leading causes of death worldwide and the number of cancer-diagnosed patients is rapidly increasing, in part due to an ageing population, and is expected to reach 22 million cases in the next two decades (Stewart 2015). Currently, the main therapeutic approaches used to treat cancer are surgery, chemotherapy, and radiotherapy, delivered separately or in various combinations (Sánchez-Santos 2012). Surgery and radiotherapy are key players for treating primary non-metastasised solid tumours, but for patients with co-morbidities that are unfit for surgery, deep-seated tumours, especially those associated with major blood vessels, or brain tumours, combined chemotherapy approaches are common.
Targeted radiotherapy with gold nanoparticles: current status and future perspectives
Nanomedicine, 2014
Radiation therapy (RT) is the treatment of cancer and other diseases with ionizing radiation. The ultimate goal of RT is to destroy all the disease cells while sparing healthy tissue. Towards this goal, RT has advanced significantly over the past few decades in part due to new technologies including: multileaf collimator-assisted modulation of radiation beams, improved computer-assisted inverse treatment planning, image guidance, robotics with more precision, better motion management strategies, stereotactic treatments and hypofractionation. With recent advances in nanotechnology, targeted RT with gold nanoparticles (GNPs) is actively being investigated as a means to further increase the RT therapeutic ratio. In this review, we summarize the current status of research and development towards the use of GNPs to enhance RT. We highlight the promising emerging modalities for targeted RT with GNPs and the corresponding preclinical evidence supporting such promise towards potential clini...