title: RGD Peptides-Conjugated Pluronic Triblock Copolymers Encapsulated with AP-2α Expression Plasmid for Targeting Gastric Cancer Therapy in Vitro and in Vivo.
abstract: Gastric cancer, a high-risk malignancy, is a genetic disease developing from a cooperation of multiple gene mutations and a multistep process. Gene therapy is a novel treatment method for treating gastric cancer. Here, we developed a novel Arg-Gly-Asp (RGD) peptides conjugated copolymers nanoparticles-based gene delivery system in order to actively targeting inhibit the growth of gastric cancer cells. These transcription factor (AP-2α) expression plasmids were also encapsulated into pluronic triblock copolymers nanoparticles which was constituted of poly(ethylene glycol)-block-poly(propylene glycol)- block-poly(ethylene glycol) (PEO-block-PPO-block-PEO, P123). The size, morphology and composition of prepared nanocomposites were further characterized by nuclear magnetic resonance (NMR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). In MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide) analysis, these nanocomposites have minor effects on the proliferation of GES-1 cells but significantly decreased the viability of MGC-803, suggesting they own low cytotoxicity but good antitumor activity. The following in vivo evaluation experiments confirmed that these nanocomposites could prevent the growth of gastric cancer cells in the tumor xenograft mice model. In conclusion, these unique RGD peptides conjugated P123 encapsulated AP-2α nanocomposites could selectively and continually kill gastric cancer cells by over-expression of AP-2α in vitro and in vivo; this exhibits huge promising applications in clinical gastric cancer therapy.
authors.affiliation: Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, China. wangwei@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China. wangwei@sysucc.org.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, China. sunpeng@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China. sunpeng@sysucc.org.cn.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China. sunpeng@sysucc.org.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangzhou 510060, China. sunpeng@sysucc.org.cn.|Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China. sunpeng@sysucc.org.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Bengbu Medical College, Anhui 233004, China. hongwei_fang163@163.com.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Fang
authors.affiliation: Department of Anatomy, Histology and Embryology, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China. wangyueminghao@126.com.
authors.forename: Yueming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China. jijiajia1999@163.com.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Ji
authors.affiliation: Department of Orthopedic Sports Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China. biochenjun@fudan.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D053761:Nanocomposites / Q000737:chemistry / Q000648:ultrastructure; D009842:Oligopeptides / Q000737:chemistry*; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism*; D020442:Poloxamer / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D013274:Stomach Neoplasms / Q000473:pathology / Q000628:therapy*; D050656:Transcription Factor AP-2 / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D011108:Polymers; D050656:Transcription Factor AP-2; D020442:Poloxamer; C047981:arginyl-glycyl-aspartic acid
keywords: AP-2α; RGD; gastric cancer; gene therapy; triblock copolymers