In vitro and in vivo study of a nanoliposomal cisplatin as a radiosensitizer

Abstract

Objective: To investigate the in vitro and in vivo radiosensitization effect of an institutionally designed nanoliposome encapsulated cisplatin (NLE-CDDP). Materials and methods: 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. Results: 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. Conclusions: Our NLE-CDDP was demonstrated to have radiosensitization with TGF of 4.28 when administrated 72 h prior to irradiation.

CD44 is a biomarker associated with human prostate cancer radiation sensitivity

“…The following parameters were calculated: a, b, and a/b value and the surviving fraction at 2 Gy (SF2) [17]. There were various definitions of sensitivity enhancement ratio (SER), including the ratio of b value [18], the ratio of the isoeffective dose at SF 0.5 [19], the ratio of the mean inactivation dose [20], the ratio of the radiation dose that reduced the surviving colonies to 37% [21], and the ratio of SF2 [22]. We used the definition that is relevant to standard fractionation of 2 Gy and calculated the SER as follows:…”

Maternal Embryonic Leucine Zipper Kinase (MELK) as a Novel Mediator and Biomarker of Radioresistance in Human Breast Cancer

“…2C). For comparison, the well-characterized radiosensitizing drug cisplatin demonstrates enhancement ratios of 1.2 to 1.3 in cancer cell lines (29,30). There was also a significant difference in the surviving fraction after 2 Gy (the dose of daily radiation used clinically for patients treated for breast cancer) in these cells ( Supplementary Fig.…”

Novel composite drug delivery system as a novel radio sensitizer for the local treatment of cervical carcinoma

“…, where V 0 is the original tumor volume (150-200 mm 3 ); k and a, coefficient; X, irradiation dose, and y tumor growth delay (TGD) time (Zhang et al, 2011). TGD was defined as the difference between the number of days required for tumor growth to reach four times its original volume (T4V0).…”