Nanoformulation of D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) diblock copolymer for siRNA targeting HIF-1α for nasopharyngeal carcinoma therapy

• Main Authors: Chen Y, Xu G, Zheng Y, Yan M, Li Z, Zhou Y, Mei L, Li X
• Format: Article
• Language: English
• Published: Dove Medical Press 2015-02-01
• Series: International Journal of Nanomedicine
• Online Access: http://www.dovepress.com/nanoformulation-of-d-alpha-tocopheryl-polyethylene-glycol-1000-succina-peer-reviewed-article-IJN

Yuhan Chen,1,* Gang Xu,1,* Yi Zheng,2–4 Maosheng Yan,1 Zihuang Li,1 Yayan Zhou,1 Lin Mei,2–4 Xianming Li1 1Department of Radiation Oncology, Second Clinical Medicine College of Jinan University, Shenzhen, Guangdong, People’s Republic of China; 2The Shenzhen Key Laboratory of Gene and Antibody Therapy, Center for Biotechnology and BioMedicine, 3Division of Life Sciences and Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong Province, People’s Republic of China; 4School of Life Sciences, Tsinghua University, Beijing, People’s Republic of China *These authors contributed equally to this work Abstract: Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor that plays an important role in the carcinogenesis and development of nasopharyngeal carcinoma. In this research, a novel biodegradable D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA)) nanoparticle (NP) was prepared as a delivery system for small interfering ribonucleic acid (siRNA) molecules targeting HIF-1α in nasopharyngeal carcinoma gene therapy. The results showed that the NPs could efficiently deliver siRNA into CNE-2 cells. CNE-2 cells treated with the HIF-1α siRNA-loaded TPGS-b-(PCL-ran-PGA) NPs showed reduction of HIF-1α expression after 48 hours of incubation via real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. The cytotoxic effect on CNE-2 cells was significantly increased by HIF-1α siRNA-loaded NPs when compared with control groups. In a mouse tumor xenograft model, the HIF-1α siRNA-loaded NPs efficiently suppressed tumor growth, and the levels of HIF-1α mRNA and protein were significantly decreased. These results suggest that TPGS-b-(PCL-ran-PGA) NPs could function as a promising genetic material carrier in antitumor therapy, including therapy for nasopharyngeal carcinoma. Keywords: TPGS-b-(PCL-ran-PGA), nanoparticles, nasopharyngeal carcinoma, hypoxia-inducible factor-1α, gene delivery