In the present study, AS1411 aptamer conjugated gold nanoclusters (GNCs) have been introduced as a targeted radiosensitizer for enhancing megavoltage radiation therapy efficacy.
The world is naturally radioactive and approximately 82% of human-absorbed radiation doses, which are out of control, arise from natural sources such as cosmic, terrestrial, and exposure from inhalation or intake radiation sources. In recent years, several international studies have been carried out, which have reported different values regarding the effect of background radiation on human health. Gamma radiation emitted from natural sources (background radiation) is largely due to primordial radionuclides, mainly 232Th and 238U series, and their decay products, as well as 40K, which exist at trace levels in the earth's crust. Their concentrations in soil, sands, and rocks depend on the local geology of each region in the world. Naturally occurring radioactive materials generally contain terrestrial-origin radionuclides, left over since the creation of the earth. In addition, the existence of some springs and quarries increases the dose rate of background radiation in some regions that are known as high level background radiation regions. The type of building materials used in houses can also affect the dose rate of background radiations. The present review article was carried out to consider all of the natural radiations, including cosmic, terrestrial, and food radiation.
Aim: Herein, the AS1411 aptamer-targeted ultrasmall gold nanoclusters (GNCs) were assessed at different aspects as a radiosensitizer. Materials & methods: AS1411 aptamer-conjugated gold nanoclusters (Apt–GNCs) efficacy was evaluated at cancer cells targeting, radiosensitizing effect, tumor targeting, and biocompatibility in breast tumor-bearing mice. Results: Flow cytometry and fluorescence microscopy exhibited more cellular uptake for Apt–GNCs in comparison with GNCs. In addition, inductively coupled plasma optical emission spectrometry results demonstrated its effective tumor targeting as the tumors’ gold content for GNCs and Apt–GNCs were 8.53 and 15.33 μg/g, respectively. Apt–GNCs significantly enhanced radiotherapy efficacy as mean tumors’ volume decreased about 39% and 9 days increase in the mice survival was observed. Both GNCs and Apt–GNCs were biocompatible. Conclusion: The Apt–GNCs is a novel and efficient radiosensitizer.
New tumor-specific contrast agents for clinical imaging and therapy for cancer are required. To this end Gd-H (Gd-hematoporphyrin), Gd-TCP (Gd-tetra-carboranylmethoxyphenyl-porphyrin), Gd-DTPA-WM53, and Gd-DTPA-9.2.27 were synthesized and administered by systemic injection to nude mice with human melanoma (MM-138) xenografts. The biodistribution T 1 relaxation times and magnetic resonance (MR) image signal enhancement of the contrast agents are presented for the first time and compared for each group of five mice. A change (20%) in T 1 relaxation times of water in human melanoma tumor xenografts was revealed 24 hours after injection of the labeled immunoconjugate Gd-DTPA-9.2.27. The percent of injected antibody or gadolinium that localized to the tumor was measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES) to be approximately 35%. A higher concentration of gadolinium was achieved compared with nonspecific compounds, indicating selective delivery of Gd-DTPA-9.2.27 to the melanoma xenografts. Porphyrin-based contrast agents (Gd-H and Gd-TCP) also showed significant uptake in melanomas. The uptake of Gd-TCP by the tumor was sufficient to deliver boron atoms into the tumor, making possible dual use for both MR imaging ( Index terms: MRI; monoclonal antibody; Gd-DTPA; Gd-porphyrins; melanoma MAGNETIC RESONANCE IMAGING (MRI) using varied pulse sequences provides a sharp contrast between tissues with different intrinsic T 1 or T 2 relaxation times. By exploiting the differences in relaxation times, images have been produced that provide previously unobtainable physiologic and mobility information (1). The use of contrast agents to shorten relaxation times and give enhanced signal intensity (SI) may extend the potential of MRI to the diagnosis of currently subclinical tumors. Two approaches are investigated to increase the specificity of MR image contrast agents by using metalloporphyrins and a monoclonal antibody coupled with Gd-DTPA.Porphyrins are a unique class of metal chelating agents that have shown selective affinity for a variety of tumors (2). The high water solubility and stability under physiological conditions (3), low propensity for causing photoxicity (4), and intracellular localization in mitochondria for more efficient tumor cell killing (5) are reasons why these complexes have been used as tumor-specific contrast agents. Tumor-specific contrast agents with potential for clinical imaging and therapy for cancer are Gd-hematoporphyrin (gadolinium-[18,13-bis (hydroxyethyl)-3,7,12,17-tetramethyl-21H, 23H porphine-2, 18-dipropionic acid]) and Gd-TCP (gadolinium-tetra-carboranylomethoxyphenyl-porphyrin).In a second approach, monoclonal antibodies against leukemia and melanoma are used. These are chelated with Gd to form the Gd immunoconjugates Gd-DTPA-WM53 and Gd-DTPA-9.2.27. These agents are tested in the nude mice model with a human melanoma (MM-138) xenograft to investigate their pharmacokinetics. The biodistribution T 1 relaxation times and signal enhancement of the contrast agen...
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