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.
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.
Department of Radiation Oncology, Second Clinical Medicine College of Jinan University, Shenzhen, Guangdong, People's Republic of China.
Yuhan
Y
Chen
Department of Radiation Oncology, Second Clinical Medicine College of Jinan University, Shenzhen, Guangdong, People's Republic of China.
Gang
G
Xu
The Shenzhen Key Laboratory of Gene and Antibody Therapy, Cente for Biotechnology and BioMedicine, Tsinghua University, Shenzhen, Guangdong Province, People's Republic of China ; Division of Life Sciences and Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong Province, People's Republic of China ; School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.
Yi
Y
Zheng
Department of Radiation Oncology, Second Clinical Medicine College of Jinan University, Shenzhen, Guangdong, People's Republic of China.
Maosheng
M
Yan
Department of Radiation Oncology, Second Clinical Medicine College of Jinan University, Shenzhen, Guangdong, People's Republic of China.
Zihuang
Z
Li
Department of Radiation Oncology, Second Clinical Medicine College of Jinan University, Shenzhen, Guangdong, People's Republic of China.
Yayan
Y
Zhou
The Shenzhen Key Laboratory of Gene and Antibody Therapy, Cente for Biotechnology and BioMedicine, Tsinghua University, Shenzhen, Guangdong Province, People's Republic of China ; Division of Life Sciences and Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong Province, People's Republic of China ; School of Life Sciences, Tsinghua University, Beijing, People's Republic of China.
Lin
L
Mei
Department of Radiation Oncology, Second Clinical Medicine College of Jinan University, Shenzhen, Guangdong, People's Republic of China.
Xianming
X
Li
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D002277:Carcinoma; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
D000970:Antineoplastic Agents; D004337:Drug Carriers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011091:Polyesters; D034741:RNA, Small Interfering; D014810:Vitamin E; C016240:polycaprolactone; D011092:Polyethylene Glycols; C014225:tocophersolan
TPGS-b-(PCL-ran-PGA); gene delivery; hypoxia-inducible factor-1α; nanoparticles; nasopharyngeal carcinoma