title: D-SP5 Peptide-Modified Highly Branched Polyethylenimine for Gene Therapy of Gastric Adenocarcinoma.
abstract: Peptide-mediated targeting of tumors has become an effective strategy for cancer therapy. Retro-inverso peptides resist protease degradation and maintain their bioactivity. We used the retro-inverso peptide D(PRPSPKMGVSVS) (D-SP5) as a targeting ligand to develop gene therapy for gastric adenocarcinoma. D-SP5 has a higher affinity for human gastric adenocarcinoma (SGC7901) cells compared with that of its parental peptide, L(SVSVGMKPSPRP) (L-SP5). Polyethylenimine (PEI)/pDNA, polyethylene glycol (mPEG)-PEI/pDNA and D-SP5-PEG-PEI/pDNA were prepared for further study. Quantitative luciferase assays showed the transfection efficiency of D-SP5-PEG-PEI/pGL(4.2) was larger compared with that of mPEG-PEI/pGL(4.2). Flow cytometry assays revealed that the apoptosis rates of SGC7901 cells treated with D-SP5-PEG-PEI/pTRAIL were larger than mPEG-PEI/pTRAIL. Western blot assays indicated that the expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) protein in SGC7901 cells treated with D-SP5-PEG-PEI/pTRAIL was higher compared with that in cells treated with mPEG-PEI/pTRAIL. In vivo pharmacodynamics study revealed that D-SP5-PEG-PEI/pTRAIL could inhibit the growth of gastric adenocarcinoma SGC7901 xenografts in nude mice. Our results demonstrate that D-SP5-PEG-PEI is a safe and efficient gene delivery vector with potential applications in antitumor gene therapy.
authors.affiliation: †Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: †Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Zuoxu
authors.initials: Z
authors.lastname: Xie
authors.affiliation: †Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Cao
authors.initials: C
authors.lastname: Xie
authors.affiliation: †Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
authors.affiliation: ‡Department of Otolaryngology-Head and Neck Surgery, Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200030, PR China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Gao
authors.affiliation: ‡Department of Otolaryngology-Head and Neck Surgery, Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai 200030, PR China.
authors.forename: Henglei
authors.initials: H
authors.lastname: Ren
authors.affiliation: †Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Man
authors.initials: M
authors.lastname: Ying
authors.affiliation: †Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.affiliation: †Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: †Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Bingxia
authors.initials: B
authors.lastname: Su
authors.affiliation: †Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Yachao
authors.initials: Y
authors.lastname: Ren
authors.affiliation: †Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010446:Peptide Fragments / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D010446:Peptide Fragments; D053221:TNF-Related Apoptosis-Inducing Ligand; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D011092:Polyethylene Glycols; D011094:Polyethyleneimine