Saha Partha Pratim, Bhowmik Tanmoy, Dasgupta Anjan Kumar, Gomes Antony
Laboratory of Toxinology & Experimental Pharmacodynamics, Department of Physiology, University of Calcutta, 92 APC Road, Kolkata 700009, India.
Department of Biochemistry, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700019, India.
Toxicol Rep. 2014 May 2;1:74-84. doi: 10.1016/j.toxrep.2014.04.007. eCollection 2014.
Research on nanoparticles has created interest among the biomedical scientists. Nanoparticle conjugation aims to target drug delivery, increase drug efficacy and imaging for better diagnosis. Toxicity profile of the nanoconjugated molecules has not been studied well. In this communication, the toxicity profile of snake venom cytotoxin (NKCT1), an antileukemic protein toxin, was evaluated after its conjugation with gold nanoparticle (GNP-NKCT1). Gold nanoparticle conjugation with NKCT1 was done with NaBH reduction method. The conjugated product GNP-NKCT1 was found less toxic than NKCT1 on isolated rat lymphocyte, mice peritoneal macrophage, in culture, which was evident from the MTT/Trypan blue assay. Peritoneal mast cell degranulation was in the order of NKCT1 > GNP-NKCT1. The cardiotoxicity and neurotoxicity were increased in case of NKCT1 than GNP-NKCT1. On isolated kidney tissue, NKCT1 released significant amount of ALP and γ-GT than GNP-NKCT1. Gold nanoconjugation with NKCT1 also reduced the lethal activity in mice. acute/sub-chronic toxicity studies in mice showed significant increase in molecular markers due to NKCT1 treatment, which was reduced by gold nanoconjugation. Histopathology study showed decreased toxic effect of NKCT1 in kidney tissue after GNP conjugation. The present study confirmed that GNP conjugation significantly decreased the toxicity profile of NKCT1. Further studies are in progress to establish the molecular mechanism of GNP induced toxicity reduction.
纳米颗粒研究引起了生物医学科学家的兴趣。纳米颗粒偶联旨在实现靶向给药、提高药物疗效以及用于成像以实现更好的诊断。纳米偶联分子的毒性特征尚未得到充分研究。在本交流中，对蛇毒细胞毒素（NKCT1，一种抗白血病蛋白毒素）与金纳米颗粒偶联后（GNP-NKCT1）的毒性特征进行了评估。采用NaBH还原法将金纳米颗粒与NKCT1进行偶联。从MTT/台盼蓝试验可以明显看出，偶联产物GNP-NKCT1在体外对分离的大鼠淋巴细胞、小鼠腹腔巨噬细胞的毒性比NKCT1小。腹腔肥大细胞脱颗粒情况为NKCT1>GNP-NKCT1。NKCT1的心脏毒性和神经毒性比GNP-NKCT1更强。在分离的肾组织上，NKCT1释放的碱性磷酸酶（ALP）和γ-谷氨酰转移酶（γ-GT）比GNP-NKCT1多。与NKCT1的金纳米偶联也降低了其对小鼠的致死活性。对小鼠进行的急性/亚慢性毒性研究表明，NKCT1处理后分子标志物显著增加，而金纳米偶联使其降低。组织病理学研究表明，GNP偶联后NKCT1在肾组织中的毒性作用减弱。本研究证实，GNP偶联显著降低了NKCT1的毒性特征。目前正在进行进一步研究以确定GNP诱导毒性降低的分子机制。
