Evaluation of the antimetastatic and antitumor activity, of antibody loaded pemetrexed nanoparticles, in DEN-HepG2 hepatocarcinoma model

S. S. Agrawal, N. Kaushik
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Abstract

Hepatocellular carcinoma (HCC) is the sixth highest incidence of cancer worldwide, accounting for 5.7% of the overall incident cases of cancer with the third leading cause of cancer-related deaths in all age group population. Matrix metalloproteinases play an important role in cancer progression, including tumor growth, invasion, metastasis, and angiogenesis, thus the drug delivery system targeting on MMP’s would be of good significance. This study aims evaluation of the antimetastatic and antitumor activity, of antibody loaded pemetrexed nanoparticles, in di-ethylnitrosamine-HepG2 hepatocarcinoma model. An orthotopic HCC model was prepared by using di-ethylnitrosamine-CCl4 as a precursor for liver cirrhosis and as carcinogen. Study concludes that the HCC model prepared was fast and equivalent to the other models present. The targeted nanoparticles prepared, has better efficacy profile with lower side effects then the free pemetrexed available in market. Low dose and high dose (20/25 mg)/kg of pemetrexed treats HCC significantly. Our results provide a basis for further study of targeted nanoparticles.
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抗体负载培美曲塞纳米颗粒在DEN-HepG2肝癌模型中的抗转移和抗肿瘤活性评价
肝细胞癌(HCC)是全球发病率第六高的癌症,占癌症总发病率的5.7%,是所有年龄组人口中癌症相关死亡的第三大原因。基质金属蛋白酶在肿瘤的生长、侵袭、转移和血管生成等肿瘤进展过程中发挥着重要作用,因此以基质金属蛋白酶为靶点的药物传递系统具有重要意义。本研究旨在评价抗体负载培美曲塞纳米颗粒在二乙基亚硝胺- hepg2肝癌模型中的抗转移和抗肿瘤活性。以二乙基亚硝胺- ccl4为肝硬化前体和致癌物制备原位肝癌模型。研究表明,所制备的肝细胞癌模型速度快,且与现有的其他肝细胞癌模型相当。所制备的靶向纳米颗粒与市场上的游离培美曲塞相比,具有更好的疗效和更低的副作用。培美曲塞低剂量和高剂量(20/ 25mg)/kg对HCC治疗效果显著。我们的研究结果为进一步研究靶向纳米颗粒提供了基础。
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