title: Pigment epithelium-derived factor gene loaded in cRGD-PEG-PEI suppresses colorectal cancer growth by targeting endothelial cells.
abstract: Pigment epithelium-derived factor (PEDF) recombinant protein has been investigated in many kinds of solid tumors due to its potent antiangiogenic activity. However, the complexity of protein purification, instability of recombinant protein and requirement of repeated injections are obstacles for the recombinant PEDF therapy for solid tumors. We successfully synthesized polyethyleneglycol-polyetherimide (PEG-PEI) and cRGD-PEG-PEI which was coupled with a cyclic RGD peptide, a special ligand for integrin αvβ3 receptor, as the vehicle for PEDF gene therapy in this study. In vitro, the competitive binding assay showed that cRGD contributed to the enhanced gene transfection efficiency of PEG-PEI in human umbilical vein endothelial cells (HUVECs). PEDF gene delivered by cRGD-PEG-PEI apparently suppressed growth of tumor with a 67.4% reduction and decreased microvessel density in nude mice bearing SW620 human colorectal xenografts. Accordingly, SW620 tumors from cRGD-PEG-PEI/PEDF-pcDNA3.1 (+)-treated mice expressed more PEDF than that of the control groups. Our study demonstrated that cRGD-PEG-PEI transported the PEDF gene into endothelia cells more efficiently than PEG-PEI, resulting in more effective inhibitory effects on tumor growth by anti-angiogenesis. Therefore, for the first time, we have explored an effective non-viral vehicle for PEDF gene therapy by targeting endothelial cells.
authors.affiliation: Department of Biochemistry, Zhongshan Medical School, Sun Yat-sen University, Guangzhou 510080, Guangdong Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Wang
authors.forename: Ya-Chao
authors.initials: YC
authors.lastname: Yao
authors.forename: Shu-Huan
authors.initials: SH
authors.lastname: Fang
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Dai
authors.forename: Hong-Hai
authors.initials: HH
authors.lastname: Hong
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
authors.forename: Xin-Tao
authors.initials: XT
authors.lastname: Shuai
authors.forename: Guo-Quan
authors.initials: GQ
authors.lastname: Gao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D005136:Eye Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D009842:Oligopeptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000031:analogs & derivatives / Q000737:chemistry; D015843:Serpins / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D004247:DNA; D005136:Eye Proteins; D009414:Nerve Growth Factors; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); C047981:arginyl-glycyl-aspartic acid