Cisplatin-conjugated gold nanoparticles as a theranostic agent for head and neck cancer (original) (raw)
Related papers
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.
Reducing the effective dose of cisplatin using gold nanoparticles as carriers
Cancer Nanotechnology, 2020
Nanotechnology is a frequent treatment for cancer. Nanomaterials are the vehicles which deliver drugs in smaller but equally effective quantities. The aim of this investigation is to synthesize gold nanoparticles, functionalize them for the transportation of cisplatin and release them to the cancer-affected area. They have the same cytotoxicity as conventional treatments but with the smallest effective quantity of cisplatin. We synthesized spherical gold nanoparticles using the Turkevich method. We functionalized them with polyethylene glycol and cisplatin, adapting the method used by Sun. Using electronic transmission microscopy, Dynamic Light Scattering and potential Z, we analyzed the size, hydrodynamic size, shape and stability of the synthesized nanoparticles. We analyzed their composition using images from scanning electronic microscopy to carry out energy dispersive spectroscopy measurements, ultraviolet/visible light spectroscopy and Fourier transform infrared spectroscopy. ...
Cancers
Combined use of chemotherapy and radiation therapy is commonly used in cancer treatment, but the toxic effects on normal tissue are a major limitation. This study assesses the potential to improve radiation therapy when combining gold nanoparticle (GNP) mediated radiation sensitization with chemoradiation compared to chemoradiation alone. Incorporation of GNPs with 2 Gy, 6 MV (megavoltage) radiation resulted in a 19 ± 6% decrease in survival of MDA-MB-231 cells. Monte-Carlo simulations were performed to assess dosimetric differences in the presence of GNPs in radiation. The results show that physics dosimetry represents a small fraction of the observed effect. The survival fraction of the cells exposed to GNPs, cisplatin, and radiation was 0.16 ± 0.007, while cells treated with cisplatin and radiation only was 0.23 ± 0.011. The presence of GNPs resulted in a 30 ± 6% decrease in the survival, having an additive effect. The concentration of the GNPs and free drug used for this study was 0.3 and 435 nM, respectively. These concentrations are relatively lower and achievable in an in vivo setting. Hence, the results of our study would accelerate the incorporation of GNP-mediated chemoradiation into current cancer therapeutic protocols in the near future.
Gold nanoparticle mediated combined cancer therapy
Cancer Nanotechnology
Background: The combined use of radiation therapy and chemotherapy is commonly being used in cancer treatment. The side effects of the treatment can be further minimized through targeted delivery of anticancer drugs and local enhancement of the radiation dose. Gold nanoparticles (GNPs) can play a significant role in this regard since GNPs can be used as radiation dose enhancers and anticancer drug carriers. Anticancer drug, bleomycin, was chosen as the model drug, since it could be easily conjugated onto GNPs through the gold-thiol bond. Methods: Gold nanoparticles of size 10 nm were synthesized using the citrate reduction method. The surface of The GNPs was modified with a peptide sequence (CKKKK-KKGGRGDMFG) containing the RGD domain and anticancer drug, bleomycin. Human breast cancer cells (MDA-MB-231) were incubated with 0.3 nM concentration of GNPdrug complex for 16 h prior to irradiation with a 2 Gy single fraction of 6 MV X-rays. After the treatment, cells were trypsinized and seeded in 60 mm dishes for clonogenic assay. Damage to DNA was probed using immunofluorescence assay. Results: Cancer cells internalized with the GNP-drug complex had a 32 ± 9% decrease in cell survival and statistically significant enhancement in DNA (deoxyribonucleic acid) damage as compared to control cells (irradiated with no GNPs) after receiving a radiation dose of 2 Gy with 6 MV photons. Conclusions: The experimental results demonstrate that GNP-mediated chemoradiation has the potential to improve cancer care in the near future through enhancement of the local radiation dose and controlled delivery of anticancer drugs.
Gold nanoparticles in radiation research: potential applications for imaging and radiosensitization
Translational cancer research, 2013
The potential of gold nanoparticles (GNPs) in therapeutic and diagnostic cancer applications is becoming increasingly recognized. These biologically compatible particles can be easily synthesized, tuned to different sizes, and functionalized by conjugation to various biologically useful materials. Efficient and specific delivery to tumor tissue can then be accomplished either by passive accumulation in leaky tumor vessels and tissue, or by directly targeting tumor-specific biomarkers. Tumor-localized GNPs can serve as both adjuvants for enhancing the efficacy of radiation therapy and also as contrast agents for various imaging modalities. In this review, we will discuss recent advancements and future potential in the application of GNP as both a radiosensitizer and an imaging contrast agent. Due to their versatility and biocompatibility, gold nanoparticles may represent a novel theranostic adjuvant for radiation applications in cancer management.
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.
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.
Gold nanoparticles as cancer theranostic agents
Nanomedicine Journal, 2019
The application of nanotechnology in medicine involves using nanomaterials to develop novel therapeutic and diagnostic modalities. Given the unique physiochemical and optical properties of gold nanoparticle (GNP) such as good biocompatibility, nontoxic nature, surface properties and comparative stability, it has been widely studied in medicine, especially as a cancer theranostic agent. This review focuses on recent progresses in the field of gold nanostructures in cancer treatment and diagnosis. As far as cancer detection is concerned, several studies have indicated that GNPs can be used for X-ray, MR and optical imaging. With regard to cancer treatment, most studies have investigated the effect of GNPs in different treatment modalities like photothermal therapy, photodynamic therapy, sonodynamic therapy, drug delivery, and radiotherapy. In this paper, we have focused on reviewing the role of GNPs in improving radiotherapy efficiency as radiosensitizers. For optimization of paramete...
Advanced Science
Radiotherapy (RT) [1] is an irreplaceable treatment strategy for effectively controlling local tumor and eradicating unresectable parts of tumor in current clinics, which has been mostly applied for combining with chemotherapy and surgical therapy. With respect to killing cancer cells, it is much unquestionable to need a high-energy dose of ionizing radiation, but the severe radiation damage for adjacent healthy tissues cannot be ignored. [2] More troubling, when reducing the radiation dose or increasing the radiation times, it would induce the emergence An ideal radiosensitizer holding an enhanced tumor retention can play an incredible role in enhancing tumor radiotherapy. Herein, a strategy of acid-triggered aggregation of small-sized gold nanoparticles (GNPs) system within tumor is proposed and the resulting GNPs aggregates are applied as a radiosensitizer in vitro and in vivo. The GNPs system with the acid-triggered aggregation achieves an enhanced GNPs accumulation and retention in cancer cells and tumors in the form of the resulted GNPs aggregates. As a consequence, the radiosensitization effect shows significant improvement in cancer radiotherapy, which is shown in the studies of DNA breakage and the comet assay, and the sensitizer enhancement ratio (SER) value of the GNPs system (1.730) with MCF-7 cancer cells is much larger than that of the single GNPs (1.16). In vivo antitumor studies reveal that the GNPs system also enhances the sensitivity of MCF-7 tumor xenograft to radiotherapy. Furthermore, the GNPs aggregates improve the signal of small GNPs in vivo photoacoustic imaging. This study provides a new strategy and insights into fabricating nanoaggregates to magnify the radiosensitive efficiency of nanosystems in cancer radiotherapy.