Khosravani Fatemeh, Mir Hamed, Mirzaei Ali, Kobarfard Farzad, Bardania Hassan, Hosseini Ebrahim
Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran.
Research Center for Noncommunicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran.
Biotechnol Appl Biochem. 2023 Apr;70(2):811-823. doi: 10.1002/bab.2401. Epub 2022 Sep 21.
During the past few years, advances in drag delivery have provided many opportunities in the treatment of various diseases and cancer. Arsenic trioxide (ATO) and Erlotinib (Erlo) are two drugs, approved by the United States Food and Drug Administration to treat cancer, but their use is limited in terms of the toxicity of ATO and the low solubility of Erlo. This study aimed to prepare arginine-glycine-aspartic acid (RGD)-decorated nanoliposomes (NLPs) containing Erlo and ATO (NLPs-ATO-Erlo-RGD) to increase the solubility and reduce the toxicity of Erlo and ATO for cancer treatment. The results of transmission electron microscopy and dynamic light scattering showed that NLPs were synthesized uniformly, with spherical shape morphology and particle sizes between 140 and 160 nm. High-performance liquid chromatography and ICP-MS results showed that about 90% of the drug was loaded in the NLPs. In comparison with NLPs-ATO-Erlo, NLPs-ATO-Erlo-RGD demonstrated considerable toxicity against the αvβ3 overexpressing PC3 cell line in the MTT experiment. It had no effect on the PANC-1 cell line. In addition, apoptosis assays using Annexin V/PI demonstrated that NLPs-ATO-Erlo-RGD generated the highest apoptotic rates in PC3 cells when compared with NLPs-ATO-Erlo and the combination of free ATO and Erlo. Furthermore, treatment with NLPs-ATO-Erlo-RGD in (p < 0.05) PC3 cell line significantly reduced EGFR level. It is concluded NLPs-ATO-Erlo-RGD as a novel drug delivery system may be a promising platform for the treatment of cancer.
在过去几年中，药物递送方面的进展为各种疾病和癌症的治疗提供了许多机会。三氧化二砷（ATO）和厄洛替尼（Erlo）是两种已被美国食品药品监督管理局批准用于治疗癌症的药物，但由于ATO的毒性和Erlo的低溶解度，它们的应用受到限制。本研究旨在制备含有Erlo和ATO的精氨酸-甘氨酸-天冬氨酸（RGD）修饰的纳米脂质体（NLPs，即NLPs-ATO-Erlo-RGD），以提高Erlo和ATO的溶解度并降低其对癌症治疗的毒性。透射电子显微镜和动态光散射结果表明，NLPs合成均匀，呈球形形态，粒径在140至160纳米之间。高效液相色谱和电感耦合等离子体质谱结果表明，约90%的药物负载在NLPs中。在MTT实验中，与NLPs-ATO-Erlo相比，NLPs-ATO-Erlo-RGD对过表达αvβ3的PC3细胞系表现出相当大的毒性。它对PANC-1细胞系没有影响。此外，使用膜联蛋白V/碘化丙啶的凋亡分析表明，与NLPs-ATO-Erlo以及游离ATO和Erlo的组合相比，NLPs-ATO-Erlo-RGD在PC3细胞中产生的凋亡率最高。此外，用NLPs-ATO-Erlo-RGD处理（p<0.05）PC3细胞系可显著降低表皮生长因子受体（EGFR）水平。得出的结论是，NLPs-ATO-Erlo-RGD作为一种新型药物递送系统可能是治疗癌症的一个有前景的平台。
