Departments of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.
Int J Nanomedicine. 2011;6:437-44. doi: 10.2147/IJN.S15997. Epub 2011 Feb 21.
To investigate the in vitro and in vivo radiosensitization effect of an institutionally designed nanoliposome encapsulated cisplatin (NLE-CDDP).
NLE-CDDP was developed by our institute. In vitro radiosensitization of NLE-CDDP was evaluated by colony forming assay in A549 cells. In vivo radiosensitization was studied with tumor growth delay (TGD) in Lewis lung carcinoma. The radiosensitization for normal tissue was investigated by jejunal crypt survival. The radiosensitization studies were carried out with a 72 h interval between drug administration and irradiation. The mice were treated with 6 mg/kg of NLE-CDDP or CDDP followed by single doses of 2 Gy, 6 Gy, 16 Gy, and 28 Gy. Sensitization enhancement ratio (SER) was calculated by D(0)s of cell survival curves for A549 cells, doses needed to yield TGD of 20 days in Lewis lung carcinoma, or D(0)s of survival curves in crypt cells in radiation alone and radiation plus drug groups.
Our NLE-CDDP could inhibit A549 cells in vitro with half maximal inhibitory concentration of 1.12 μg/mL, and its toxicity was 2.35 times that observed in CDDP. For in vitro studies of A549 cells, SERs of NLE-CDDP and CDDP were 1.40 and 1.14, respectively, when combined with irradiation. For in vivo studies of Lewis lung carcinoma, the strongest radiosensitization was found in the 72 h interval between NLE-CDDP and irradiation. When given 72 h prior to irradiation, NLE-CDDP yielded higher radiosensitization than CDDP (SER of 4.92 vs 3.21) and slightly increased injury in jejunal crypt cells (SER of 1.15 vs 1.19). Therefore, NLE-CDDP resulted in a higher TGF than did CDDP (4.28 vs 2.70) when SERs were compared between experiments in vivo and in jejunal crypt cell studies.
Our NLE-CDDP was demonstrated to have radiosensitization with TGF of 4.28 when administrated 72 h prior to irradiation.
研究本单位研制的载顺铂纳米脂质体（NLE-CDDP）的体外和体内放射增敏作用。
本单位研制的 NLE-CDDP。采用集落形成试验评价 NLE-CDDP 的体外放射增敏作用。采用Lewis 肺癌肿瘤生长延迟（TGD）研究体内放射增敏作用。采用空肠隐窝存活研究正常组织的放射增敏作用。药物与照射间隔 72 小时进行放射增敏研究。用 6mg/kg 的 NLE-CDDP 或 CDDP 处理小鼠，然后给予单次 2Gy、6Gy、16Gy 和 28Gy 照射。A549 细胞存活曲线的 D（0）、Lewis 肺癌 TGD 达 20 天所需剂量或单纯照射和照射加药物组隐窝细胞存活曲线的 D（0）计算增敏增强比（SER）。
本研究的 NLE-CDDP 体外抑制 A549 细胞的半数抑制浓度为 1.12μg/ml，其毒性是 CDDP 的 2.35 倍。对于 A549 细胞的体外研究，NLE-CDDP 和 CDDP 与照射联合时的 SER 分别为 1.40 和 1.14。对于 Lewis 肺癌的体内研究，NLE-CDDP 和照射之间的 72 小时间隔发现最强的放射增敏作用。照射前 72 小时给予 NLE-CDDP 时，其放射增敏作用高于 CDDP（SER 为 4.92 比 3.21），空肠隐窝细胞损伤略增加（SER 为 1.15 比 1.19）。因此，当比较体内实验和空肠隐窝细胞研究中的 SER 时，NLE-CDDP 的 TGF 比 CDDP 高（4.28 比 2.70）。
本研究结果表明，NLE-CDDP 在照射前 72 小时给药时，TGF 为 4.28，具有放射增敏作用。
