Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Int J Nanomedicine. 2010 Feb 2;5:63-75. doi: 10.2147/ijn.s8595.
Due to their unique properties, Anticancer dendrimer-based drugs have been displaying promising results in both in vitro and in vivo in the treatment of cancerous cells, as compared to the traditional polymers. In this report, two conjugates (G1+Pt and G2+Pt) of cisplatin [cis-diaminedichloroplatinum; (CDDP)] with two generations (G1, G2) of a biocompatible anionic dendrimer were prepared in an aqueous media. Their potential cytotoxic effects, in two sensitive cancer cell lines HT1080 and CT26 together with one resistant cancer cell line SKOV3, using MTT (methyl thiazolyl tetrazolium) assay were examined. Hemolytic impacts and cell death mechanisms of the conjugates on human blood and HT1080 cell line were also investigated. The conjugate G2+Pt showed greater toxicity up to 9x and 2x in the sensitive and resistant cell lines (IC(50) comparison, inhibitory concentration) respectively when compared to the parent drug. The G1+Pt conjugate showed greater toxicity only in the sensitive HT1080 (2x) and CT26 (3.7x) cell lines. Moreover, the G1+Pt conjugate was less toxic approximately one third of the cisplatin in SKOV3 after 48 hrs of incubation. In summary, the G2+Pt conjugate had greater toxicity than the G1+Pt conjugate and cisplatin, based on the in vitro results. Approximately the same hemolysis behavior was observed for both conjugates and cisplatin. Both apoptosis and necrosis mechanisms (about 2x more than cisplatin) were attributed to conjugates and cisplatin in a direct correlation between the concentration and the degree of cell death. In conclusion, these conjugates with such high potency and minimum hemolysis would be suitable candidates for use against these cancerous cell lines as efficient and novel antitumor agents.
由于其独特的性质，与传统聚合物相比，基于抗癌树突状聚合物的药物在治疗癌细胞的体外和体内都显示出了有希望的结果。在本报告中，在水介质中制备了两种顺铂[顺二氨二氯铂;（CDDP）]与两代（G1，G2）生物相容阴离子树突状聚合物的缀合物（G1 + Pt 和 G2 + Pt）。使用 MTT（甲基噻唑基四唑）测定法，研究了它们在两种敏感癌细胞系 HT1080 和 CT26 以及一种耐药癌细胞系 SKOV3 中的潜在细胞毒性作用。还研究了缀合物对人血和 HT1080 细胞系的溶血作用和细胞死亡机制。与母体药物相比，缀合物 G2 + Pt 在敏感和耐药细胞系中的毒性分别高达 9 倍和 2 倍（IC（50）比较，抑制浓度）。G1 + Pt 缀合物仅在敏感 HT1080（2 倍）和 CT26（3.7 倍）细胞系中显示出更高的毒性。此外，在孵育 48 小时后，G1 + Pt 缀合物在 SKOV3 中的毒性约为顺铂的三分之一。总之，基于体外结果，G2 + Pt 缀合物比 G1 + Pt 缀合物和顺铂具有更高的毒性。两种缀合物和顺铂的溶血行为大致相同。凋亡和坏死机制（比顺铂高约 2 倍）归因于两种缀合物和顺铂，与细胞死亡的浓度和程度之间存在直接相关性。总之，这些具有高效力和最小溶血的缀合物将是针对这些癌细胞系的有效和新型抗肿瘤药物的合适候选物。
