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

IF 1.4 Q4 NANOSCIENCE & NANOTECHNOLOGY Nanomedicine Journal Pub Date : 2020-10-01 DOI:10.22038/NMJ.2020.07.00004
M. Mirzaei, M. Akbari, M. Mohagheghi, S. Tavangar, Bita Mehravi, M. Ardestani
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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.
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Gd(III)阴离子线型球状树状大分子第二代G2-C595纳米探针的体内外毒性和组织病理学评价
目的:毒性组织病理学研究用于评估纳米颗粒在生物体暴露中的毒性影响。本研究旨在评价Gd(III)-阴离子线性球形树突状物第二代G2-C595 (Gd[III]树突状物G2-C595)对比纳米探针在暴露于许多裸鼠器官和生物体方面的潜在纳米细胞毒性影响。此外,我们还评估了Gd(III)-树突状分子G2-C595纳米探针作为新型磁共振成像(MRI)纳米造影剂对人乳腺癌细胞系(MCF-7)和人胚胎肾细胞系(HEK-293)的潜力。材料与方法:将钆(Gd[III])负载于树状大分子G2上,与C595单克隆抗体偶联生成Gd(III)-树状大分子G2-C595,测定其对MUC1有益肿瘤的影响。体外和体内研究了Gd(III)-树突分子G2-C595纳米探针对HEK-293细胞的细胞毒作用。此外,将Gd(III)-树突状分子G2-C595纳米探针应用于携带MCF-7肿瘤的裸鼠,探讨其对体内肿瘤模型的特异性活性。结果:Gd(III)-树突分子G2-C595造影剂纳米探针影响MCF-7的细胞毒性,对HEK-293细胞、肾脏、心、肺、脑、肝组织等器官无体内毒性作用。结论:Gd(III)-树突状分子G2和Gd(III)-树突状分子G2- c595对小鼠HEK-293细胞及心、肝、脑组织均无毒性作用。此外,Gd(III)-树突状分子G2-C595对体内肿瘤模型具有特异性抗作用。因此,Gd(III)-树状大分子G2-C595纳米探针是一种新型有效的MR造影剂和抗肿瘤载体。此外,Gd(III)-枝状大分子G2-C595纳米探针具有良好的生物相容性和安全性,对正常器官功能没有影响。
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来源期刊
Nanomedicine Journal
Nanomedicine Journal NANOSCIENCE & NANOTECHNOLOGY-
CiteScore
3.40
自引率
0.00%
发文量
0
审稿时长
12 weeks
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