A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation

Hua-shan Shi¹,^* Xiang Gao,^1,3,* Dan Li,^1,* Qiong-wen Zhang,¹ Yong-sheng Wang,² Yu Zheng,¹ Lu-Lu Cai,1 Ren-ming Zhong,² Ao Rui,¹ Zhi-yong Li,¹ Hao Zheng,¹ Xian-cheng Chen,¹ Li-juan Chen,<sup>1

1</sup>State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medicine School, Sichuan University, Chengdu, Sichuan, People's Republic of China; ²State Key Laboratory of Biotherapy and Department of Thoracic Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China; ³Deparment of Pathophysiology, College of Preclinical and Forensic Medical Sciences, Sichuan University, Chengdu, People's Republic of China

*These authors contributed equally to this work

Abstract: 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.

Keywords: liposomes, curcumin, lung cancer