Research Center for Cell Fate Control (RCCFC), College of Pharmacy, Sookmyung Women's University , Seoul , South Korea.
Drug Dev Ind Pharm. 2014 Apr;40(4):470-6. doi: 10.3109/03639045.2013.768631. Epub 2013 Apr 24.
Gemcitabine-loaded TSL (Gem-TSL) was used in combination with hyperthermia (HT) to treat the colon adenocarcinoma-bearing BALB/c mice for improved anticancer effect following intravenous administration.
A new temperature-sensitive liposome (TSL), composed of DPPC:DMPC:DSPC (4:1:1 molar ratio) releasing the encapsulated gemcitabine (Gem) at 41 °C, was developed and evaluated for enhanced antitumor efficacy both in vitro and in vivo.
Drug release from the TSL was sharply increased at 41 °C and in vitro cytotoxicity of Gem-TSL in colon adenocarcinoma cells (CT-26) was 10 times higher than the free drug (IC50 = 0.3 μM versus 3 μM). Apoptosis seemed to be the main mechanism of cell death as the treatment of the cells with Gem-TSL increased the caspse-3/7 activity by 1.5-fold and also caused the fragmentation of chromatin DNA. Gem-TSL suppressed the tumor growth in CT-26-bearing BALB/c mice more stronger than the free gemcitabine after intravenous administration. Moreover, this in vivo antitumor efficacy of Gem-TSL was further increased when HT was added.
This study suggests that this new TSL-Gem formulation could serve as a new chemotherapy modality together with HT.
载有吉西他滨的 TSL（Gem-TSL）与热疗（HT）联合应用于荷结肠腺癌的 BALB/c 小鼠，以期提高静脉给药后的抗癌效果。
开发了一种新的温度敏感脂质体（TSL），由 DPPC：DMPC：DSPC（4：1：1 摩尔比）组成，在 41°C 时释放包封的吉西他滨（Gem），并对其进行了评估体外和体内增强抗肿瘤功效。
TSL 中的药物释放在 41°C 时急剧增加，载有吉西他滨的 TSL（Gem-TSL）对结肠腺癌细胞（CT-26）的体外细胞毒性比游离药物高 10 倍（IC50 = 0.3 μM 对 3 μM）。细胞凋亡似乎是细胞死亡的主要机制，因为用 Gem-TSL 处理细胞可使 caspase-3/7 活性增加 1.5 倍，并导致染色质 DNA 的片段化。与静脉注射游离吉西他滨相比，Gem-TSL 能更有效地抑制 CT-26 荷瘤 BALB/c 小鼠的肿瘤生长。此外，当加入 HT 时，这种 Gem-TSL 的体内抗肿瘤疗效进一步增强。
本研究表明，这种新的 TSL-Gem 制剂可与 HT 一起作为一种新的化疗方法。
