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

Hypoxia-inducible factor-1alpha (HIF-1alpha) 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-alpha-tocopheryl polyethylene glycol 1000 succinate-b-poly(epsilon-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-1alpha 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-1alpha siRNA-loaded TPGS-b-(PCL-ran-PGA) NPs showed reduction of HIF-1alpha 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-1alpha siRNA-loaded NPs when compared with control groups. In a mouse tumor xenograft model, the HIF-1alpha siRNA-loaded NPs efficiently suppressed tumor growth, and the levels of HIF-1alpha 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.