title: Promising Nanocarriers for PEDF Gene Targeting Delivery to Cervical Cancer Cells Mediated by the Over-expressing FRα.
abstract: Cervical cancer presents extremely low PEDF expression which is associated with tumor progression and poor prognosis. In this study, folate receptor α (FRα)-targeted nano-liposomes (FLP) were designed to enhance the anti-tumor effect by targeting delivery of exogenous PEDF gene to cervical cancer cells. The targeting molecule F-PEG-Chol was firstly synthesized by a novel simpler method. FLP encapsulating PEDF gene (FLP/PEDF) with a typical lipid-membrane structure were prepared by a film dispersion method. The transfection experiment found FLP could effectively transfect human cervical cancer cells (HeLa cells). FLP/PEDF significantly inhibited the growth of HeLa cells and human umbilical vein endothelial cells (HUVEC cells) and suppressed adhension, invasion and migration of HeLa cells in vitro. In the abdominal metastatic tumor model of cervical cancer, FLP/PEDF administered by intraperitoneal injection exhibited a superior anti-tumor effect probably due to the up-regulated PEDF. FLP/PEDF could not only sharply reduce the microvessel density but also dramatically inhibit proliferation and markedly induce apoptosis of tumor cells in vivo. Moreover, the preliminary safety investigation revealed that FLP/PEDF had no obvious toxicity. These results clearly showed that FLP were desired carriers for PEDF gene and FLP/PEDF might represent a potential novel strategy for gene therapy of cervical cancer.
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.
authors: Yuhan
authors: Y
authors: Yang
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.|College of Pharmacy, Southwest University for Nationalities, Chengdu 610041, China.
authors: Lili
authors: L
authors: He
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.
authors: Yongmei
authors: Y
authors: Liu
authors: Chemistry and Life Science College, Chengdu Normal University, Chengdu 611130, China.
authors: Shan
authors: S
authors: Xia
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.
authors: Aiping
authors: A
authors: Fang
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.
authors: Yafei
authors: Y
authors: Xie
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.
authors: Li
authors: L
authors: Gan
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.
authors: Zhiyao
authors: Z
authors: He
authors: Department of Pathology/Collaborative Innovation Center of Biotherapy, Medical School of Nankai University, Tianjin 300071, China.
authors: Xiaoyue
authors: X
authors: Tan
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.
authors: Chunling
authors: C
authors: Jiang
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.
authors: Aiping
authors: A
authors: Tong
authors: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu 610041, China.
authors: Xiangrong
authors: X
authors: Song
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage; D005136:Eye Proteins / Q000235:genetics* / Q000627:therapeutic use; D005260:Female; D058975:Folate Receptor 1 / Q000235:genetics* / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009414:Nerve Growth Factors / Q000235:genetics* / Q000627:therapeutic use; D015843:Serpins / Q000235:genetics* / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D004337:Drug Carriers; D005136:Eye Proteins; D058975:Folate Receptor 1; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor