State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Int J Nanomedicine. 2012;7:2601-11. doi: 10.2147/IJN.S31439. Epub 2012 May 24.
Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.
放射性肺炎（RP）是胸部放射治疗中的一种重要剂量限制毒性。先前的研究表明，姜黄素可用于治疗炎症和癌症，这表明姜黄素可能预防 RP 并使癌细胞对辐射敏感。然而，姜黄素的临床进展受到其口服后较差的水溶性和低生物利用度的限制。在这里，开发了一种水溶性脂质体姜黄素系统，通过小鼠模型以静脉给药方式研究其预防和敏化作用。结果表明，脂质体姜黄素抑制了核因子-κB 通路，并下调了由胸部照射诱导的炎性因子，包括肿瘤坏死因子-α、白细胞介素（IL）-6、IL-8 和转化生长因子-β。此外，脂质体姜黄素与放疗联合治疗增加了体内肿瘤内的细胞凋亡和对放疗的微血管反应。在小鼠肺癌（LL/2）模型中也观察到肿瘤生长的显著抑制。在小鼠中未观察到明显的毒性。目前的结果表明，脂质体姜黄素可以有效减轻 RP，减少肺纤维化，并使 LL/2 细胞对辐射敏感。这项研究还表明，系统给予脂质体姜黄素是安全的，值得进一步临床应用研究。
