Thermosensitive <i>In Situ</i> Gel Containing Luteolin Micelles is a Promising Efficient Agent for Colorectal Cancer Peritoneal Metastasis Treatment
Yuzhu Hu, Xiaoye Chen, Zongyuan Li, Songping Zheng, Yongzhong Cheng
Abstract
Luteolin (Lut) is a natural flavonoid mainly extracted from vegetables and fruits. Lut shows great anti-tumor potential in many malignant cancers, which are hindered by poor water solubility and low bioavailability. Peritoneal metastasis is a challenge for colorectal cancer treatment, usually indicating unfavorable prognosis of patients. Methoxy poly(ethylene glycol)-poly( ε -caprolactone) micelles containing Luteolin (Lut-M) and thermosensitive Pluronic ® F127 coated Lut-M (Lut-M-F127) were synthesized and applied in the local therapy of colorectal cancer. Drug release study of Lut-M-F127 and Lut-M suggested extended drug release, and the release of Lut from Lut-M-F127 was slower than Lut-M. It was also proved that Lut-M-F127 could transit from solution to gel at body temperature. Moreover, both Lut-Free and Lut-M micelles were capable of inducing tumor cell apoptosis and reducing cell viability in vitro . Our results further demonstrated the therapeutic effect of Lut-M-F127 treatment was much better than that of Lut-M treatment in vivo . Lut-M-F127 has shown strong ability to promote tumor apoptosis, suppress tumor proliferation and block tumor angiogenesis. In summary, Lut-M-F127 formulation may be a very promising treatment option for peritoneal metastasis in colorectal cancer in the future.