Department of Zoology, Savitribai Phule Pune University, Pune, Maharashtra, India.
Curr Pharm Biotechnol. 2020;21(14):1479-1488. doi: 10.2174/1389201021666200519101221.
NN-32 toxin, which was obtained from Naja naja venom and showed cytotoxicity on cancer cell lines. As the toxicity of NN-32 is the main hurdle in the process of drug development; hence, we have conjugated NN-32 toxin with gold nanoparticles (GNP-NN-32) in order to decrease the toxicity of NN-32 without reducing its efficacy, GNP-NN-32 alleviated the toxicity of NN-32 in in vitro studies during the course of earlier studies. In continuation, we are evaluating in vivo toxicity profile of NN-32 and GNP-NN-32 in the present study.
To study in vivo toxicity profile of NN-32 and nanogold conjugated GNP-NN-32 from Naja naja venom.
We have carried out in vivo acute toxicity study to determine LD50 dose of GNP-NN-32, in vivo sub-chronic toxicity for 30 days, haematology, serum biochemical parameters and histopathology study on various mice tissues and in vitro cellular and tissue toxicity studies.
The LD50 dose of GNP-NN-32 was found to be 2.58 mg/kg (i.p.) in Swiss male albino mice. In vivo sub-chronic toxicity showed significantly reduced toxicity of GNP-NN-32 as compared to NN-32 alone.
In vitro cellular toxicity studies on human lymphocyte and mouse peritoneal macrophage showed significant inhibition of cells by NN-32 alone.
Conjugated GNP-NN-32 toxin showed less in vivo toxicity as compared to pure NN-32.
NN-32 毒素来源于眼镜蛇毒液，对癌细胞系具有细胞毒性。由于 NN-32 的毒性是药物开发过程中的主要障碍；因此，我们将 NN-32 毒素与金纳米粒子（GNP-NN-32）缀合，以降低 NN-32 的毒性而不降低其功效，在早期研究过程中，GNP-NN-32 在体外研究中减轻了 NN-32 的毒性。在此基础上，我们在本研究中评估了 NN-32 和 GNP-NN-32 的体内毒性特征。
研究来自眼镜蛇毒液的 NN-32 和纳米金缀合的 GNP-NN-32 的体内毒性特征。
我们进行了体内急性毒性研究，以确定 GNP-NN-32 的 LD50 剂量，进行了 30 天的体内亚慢性毒性研究，进行了血液学、血清生化参数和各种小鼠组织的组织病理学研究以及体外细胞毒性和组织毒性研究。
GNP-NN-32 的 LD50 剂量在瑞士雄性白化小鼠中为 2.58mg/kg（ip）。体内亚慢性毒性研究表明，与单独的 NN-32 相比，GNP-NN-32 的毒性明显降低。
单独的 NN-32 对人淋巴细胞和小鼠腹腔巨噬细胞的体外细胞毒性研究显示出对细胞的显著抑制作用。
与纯 NN-32 相比，缀合的 GNP-NN-32 毒素显示出较低的体内毒性。
