title: Targeting effect of PEGylated liposomes modiﬁed with the Arg-Gly-Asp sequence on gastric cancer.
abstract: Previous studies have demonstrated that the α5β1 integrin-mediated interaction with fibronectin (FN) occurs through the Arg-Gly-Asp (RGD) cell-binding sequence in repeat III10. Indocyanine green (ICG) is a near-infrared (NIR) optical dye that has been approved by the US Food and Drug Administration. In the present study, we developed an RGD-modiﬁed PEGylated liposome-encapsulated ICG (RGD-PLS-ICG) system mediated by integrin. RGD was conjugated covalently to the distal end of DSPE-PEG2000-NH2 lipid by amide binding. The characteristics and stability of the prepared liposomes were assessed. In vitro, SGC7901 cells with high expression of integrin α5β1 were selected by polymerase chain reaction (PCR) and western blotting. To confirm the targeting efficacies to gastric cancer, coumarin-6 was encapsulated as a ﬂuorescent probe for in vitro study, and the targeting effect of RGD was detected by flow cytometry and confocal microscopy. In vivo, the bio distribution of RGD-PLS-ICG was studied by an in vivo imaging system in the tumor model. RGD-PLS-ICG and PLS-ICG had a higher UV absorbance spectrum and stability than free-ICG. Confocal microscopy and ﬂow cytometry demonstrated that RGD-PLS-encapsulated coumarin-6 was efficiently associated with the SGC7901 cells, while limited interaction was found for the other groups. Moreover, the in vivo imaging of the liposomes indicated that RGD-PLS-ICG achieved more accumulation in the tumor tissues when compared with PLS-ICG. The significant in vitro and in vivo results suggest that RGD-PLS-ICG may be a promising fluorescent dye delivery system for targeting gastric cancer cell overexpression of integrin.
authors.affiliation: Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Wenxian
authors.initials: W
authors.lastname: Guan
mesh_terms: D058948:Cell Tracking; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007208:Indocyanine Green / Q000008:administration & dosage / Q000737:chemistry; D039081:Integrin alpha5beta1 / Q000096:biosynthesis / Q000235:genetics; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure*; D013844:Thiazoles / Q000008:administration & dosage / Q000737:chemistry
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D003374:Coumarins; D005353:Fibronectins; D039081:Integrin alpha5beta1; D008081:Liposomes; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; D013844:Thiazoles; C517282:coumarin 6; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D007208:Indocyanine Green