Department of Chemistry, Faculty of Science, Kuwait University, Kuwait, Safat, Kuwait.
Cardiovascular and Metabolic Sciences Department, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio, USA.
Drug Deliv. 2022 Dec;29(1):2206-2216. doi: 10.1080/10717544.2022.2096713.
Cancer is a leading cause of death worldwide and affects society in terms of the number of lives lost. Current cancer treatments are based on conventional chemotherapy which is nonspecific in targeting cancer. Therefore, intensive efforts are underway to better target cancer-specific cells while minimizing the side effects on healthy tissues by using LDL particles as active drug delivery vehicles. The goal is to encapsulate anticancer agents thiosemicarbazone metal-ligand complexes into LDL particles to increase the cytotoxic effect of the agent by internalization through LDL receptors into MCF7, A549, and C42 cancer cell lines as segregate models for biological evaluations targeting tubulin. Zeta potential data of LDL-particles encapsulated anticancer agents showed an acceptable diameter range between 66-91 nm and uniform particle morphology. The results showed cell proliferation reduction in all tested cell lines. The IC values of LDL encapsulated thiosemicarbazone metal-ligand complexes treated with MCF7, A549, and C42 ranged between 1.18-6.61 µM, 1.17-9.66 µM, and 1.01-6.62 µM, respectively. Western blot analysis showed a potent decrease in tubulin expression when the cell lines were treated with LDL particles encapsulated with thiosemicarbazone metal-ligand complexes as anticancer agents. In conclusion, the data provide strong evidence that LDL particles are used as an active drug delivery strategy for cancer therapy.
癌症是全球主要的死亡原因之一,对社会造成了生命损失。目前的癌症治疗方法基于常规的化疗,这种方法在靶向癌症方面是非特异性的。因此,人们正在积极努力,通过使用 LDL 颗粒作为活性药物输送载体,更好地靶向特定的癌细胞,同时最大限度地减少对健康组织的副作用。目标是将抗癌剂噻唑烷酮金属配体复合物包封到 LDL 颗粒中,通过 LDL 受体内化到 MCF7、A549 和 C42 癌细胞系中,增加药物的细胞毒性作用,作为针对微管的生物评价的分离模型。包封抗癌剂的 LDL 颗粒的 zeta 电位数据显示,可接受的直径范围在 66-91nm 之间,并且具有均匀的颗粒形态。结果表明,所有测试的细胞系的细胞增殖都减少了。用 MCF7、A549 和 C42 处理的 LDL 包封的噻唑烷酮金属配体复合物的 IC 值分别在 1.18-6.61µM、1.17-9.66µM 和 1.01-6.62µM 之间。Western blot 分析表明,当用 LDL 颗粒包封噻唑烷酮金属配体复合物作为抗癌剂处理细胞系时,微管蛋白表达明显下降。总之,这些数据提供了强有力的证据,表明 LDL 颗粒可作为癌症治疗的一种活性药物输送策略。