In vitro and in vivo toxicity and histopathological evaluation of Gd(III)anionic Linear globular dendrimer second-generation G2-C595 nanoprobe

Document Type: Research Paper

Authors

1 Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Iran Ministry of Health and Medical Education, Deputy Ministry for Education, Tehran, Iran

3 Cancer Institute Research Center, Tehran University of Medical Sciences, Tehran, Iran

4 Department of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

6 Department of Radiopharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

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.

Keywords


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