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In Vitro and in Vivo Toxicity and Histopathological Evaluation of Gd(Iii)Anionic Linear Globular Dendrimer Second-Generation G2-C595 Nanoprobe Publisher



Mirzaei M1, 2 ; Akbari ME1 ; Mohagheghi MA3 ; Tavangar SM4 ; Mehravi B5 ; Ardestani MS6
Authors
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Authors Affiliations
  1. 1. Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. Iran Ministry of Health and Medical Education, Deputy Ministry for Education, Tehran, Iran
  3. 3. Cancer Institute Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Radiopharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: Nanomedicine Journal Published:2020


Abstract

Objective(s): Toxico-histopathological studies are used to assess the toxic impacts of nanoparticles in organism exposure. The present study aimed to evaluate the prospective nano-cytotoxicity impacts of Gd(III)-anionic linear globular dendrimer second-generation G2-C595 (Gd[III] dendrimer G2-C595) contrast nanoprobe in terms of the exposure of many nude mice organs and organisms. In addition, we assessed the potential of the Gd(III)-dendrimer G2-C595 nanoprobe as a novel magnetic resonance imaging (MRI) nano-contrast agent for the human breast cancer cell line (MCF-7) and human embryonic kidney cell line (HEK-293). Materials and Methods: Gadolinium (Gd[III]) was loaded with dendrimer G2 and conjugated with the C595 monoclonal antibody to generate the Gd(III)-dendrimer G2-C595 to determine the impact on MUC1 beneficial cancer tumors. The cytotoxic effects of the Gd(III)-dendrimer G2-C595 nanoprobe on the HEK-293 cells were also investigated in-vitro and in-vivo. In addition, the Gd(III)-dendrimer G2-C595 nanoprobe was used on nude mice bearing the MCF-7 tumors to explore its specific activity against the in-vivo model of cancer. Results: The Gd(III)-dendrimer G2-C595 contrast nanoprobes affected the cytotoxicity of MCF-7, and no in-vivo toxicity was induced in the HEK-293 cells, kidneys, heart, lungs, brain, liver tissues, and other organs. Conclusion: According to the results, the Gd(III)-dendrimer G2 and Gd(III)-dendrimer G2-C595 induced no toxicity in the HEK-293 cells and heart, liver, and brain tissues of mice. In addition, the Gd(III)-dendrimer G2-C595 showed specific anti-action against the in-vivo tumor model. Therefore, the Gd(III)-dendrimer G2-C595 nanoprobe is highly recommended as a novel and effective MR contrast agent and antitumor carrier agent. Furthermore, the Gd(III)-dendrimer G2-C595 nano-sized probes demonstrated excellent biocompatibility and safety with no impact on normal organ functioning. © Mashhad University of Medical Sciences. All Rights Reserved.