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

• Published in: International journal of nanomedicine Vol. 10; no. default; pp. 1375 - 1386
• Main Authors: Chen, Yuhan, Xu, Gang, Zheng, Yi, Yan, Maosheng, Li, Zihuang, Zhou, Yayan, Mei, Lin, Li, Xianming
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2015; Dove Press; Dove Medical Press
• Subjects: Analysis; Animals; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Cancer; Carcinoma; Cell Line, Tumor; Cell Survival - drug effects; Development and progression; Drug Carriers - chemistry; Drug therapy; gene delivery; Genetic aspects; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; hypoxia-inducible factor-1α; Mice; nanoparticles; Nanoparticles - chemistry; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Original Research; Physiological aspects; Polyesters - chemistry; Polyethylene glycol; Polyethylene Glycols - chemistry; Properties; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; RNA, Small Interfering - pharmacology; TPGS-b-(PCL-ran-PGA); Vitamin E - analogs & derivatives; Vitamin E - chemistry; China; gene delivery; nasopharyngeal carcinoma; hypoxia-inducible factor-1α; nanoparticles; TPGS-b-(PCL-ran-PGA)
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S76092

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.