Karimi Ali, Erfan Mohammad, Mortazavi Seyed Alireza, Ghorbani-Bidkorbeh Fatemeh, Landi Behnaz, Kobarfard Farzad, Shirazi Farshad H
Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2019 Fall;18(Suppl1):221-236. doi: 10.22037/ijpr.2020.14484.12423.
Our goal is to reduce the release rate of methotrexate (MTX) and increase cell death efficiency.Carboxylated multi-walled carbon nanotubes (MWCNT-COOH) were functionalized with MTX as a cytotoxic agent, FA as a targeting moiety and polyethylene amine (PEI) as a hydrophilic agent. Ultimately, MWCNT-MTX and MWCNT-MTX-PEI-FA were synthesized. Methotrexate release studies were conducted in PBS and cytotoxic studies were carried out by means of the MTT tassay. Methotrexate release studies from these two carriers demonstrated that the attachment of PEI-FA onto MWCNT-MTX reduces the release rate of methotrexate. The IC50 of MWCNT-MTX-PEI-FA and MWCNT-MTX have been calculated as follows: 9.89 ± 0.38 and 16.98 ± 1.07 µg/mL, respectively. Cytotoxic studies on MWCNT-MTX-PEI-FA and MWCNT-MTX in the presence of an IR laser showed that at high concentrations, they had similar toxicities due to the MWCNT's photothermal effect. Targeting effect studies in the presence of the IR laser on the cancer cells have shown that MWCNT-MTX-PEI-FA, MWCNT-MTX, and f-MWCNT have triggered the death of cancer cells by 55.11 ± 1.97%, 49.64 ± 2.44%, and 37 ± 0.70%, respectively. The release profile of MTX in MWCNT-MTX-PEI-FA showed that the presence of PEI acts as a barrier against release and reduces the MTX release rate. In the absence of a laser, MWCNT-MTX-PEI-FA exhibits the highest degree of cytotoxicity. In the presence of a laser, the cytotoxicity of MWCNT-MTX and MWCNT-MTX-PEI-FA has no significant difference. Targeting studies have shown that MWCNT-MTX-PEI-FA can be absorbed by cancer cells exclusively.
我们的目标是降低甲氨蝶呤(MTX)的释放速率并提高细胞死亡效率。羧基化多壁碳纳米管(MWCNT-COOH)用MTX作为细胞毒性剂、FA作为靶向部分以及聚乙烯胺(PEI)作为亲水剂进行功能化。最终,合成了MWCNT-MTX和MWCNT-MTX-PEI-FA。在PBS中进行了甲氨蝶呤释放研究,并通过MTT法进行了细胞毒性研究。来自这两种载体的甲氨蝶呤释放研究表明,将PEI-FA附着到MWCNT-MTX上可降低甲氨蝶呤的释放速率。MWCNT-MTX-PEI-FA和MWCNT-MTX的IC50计算如下:分别为9.89±0.38和16.98±1.07μg/mL。在红外激光存在下对MWCNT-MTX-PEI-FA和MWCNT-MTX进行的细胞毒性研究表明,在高浓度下,由于MWCNT的光热效应,它们具有相似的毒性。在红外激光存在下对癌细胞进行的靶向效应研究表明,MWCNT-MTX-PEI-FA、MWCNT-MTX和f-MWCNT分别使癌细胞死亡率达到55.11±1.97%、49.64±2.44%和37±0.70%。MWCNT-MTX-PEI-FA中MTX的释放曲线表明,PEI的存在起到了阻止释放的屏障作用并降低了MTX的释放速率。在没有激光的情况下,MWCNT-MTX-PEI-FA表现出最高程度的细胞毒性。在有激光的情况下,MWCNT-MTX和MWCNT-MTX-PEI-FA的细胞毒性没有显著差异。靶向研究表明,MWCNT-MTX-PEI-FA可以被癌细胞特异性吸收。