title: Specific cell targeting with APRPG conjugated PEG-PLGA nanoparticles for treating ovarian cancer.
abstract: Good biocompatibility, specific tumor targeting, effective drug loading capacity and persistence in the circulation in vivo are imperative prerequisites for the antitumor efficiency of nanoparticles and their further clinical application. In this study, APRPG (Ala-Pro-Arg-Pro-Gly) peptide-modified poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) nanoparticles (NP-APRPG) encapsulating inhibitors of angiogenesis (TNP-470) (TNP-470-NP-APRPG) were fabricated. TNP-470-NP-APRPG was designed to feature maleimide-PEG-PLA and mPEG-PLA as carrier materials, the APRPG peptide for targeting angiogenesis, PEG for prolonging circulation in vivo and PLA for loading TNP-470. TNP-470-NP-APRPG was confirmed to be approximately 130 nm in size with negative ζ-potential (-14.3 mV), narrow distribution (PDI = 0.27) and spherical morphology according to dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. In addition, X-ray photoelectron spectra (XPS) analyses confirmed 7.73% APRPG grafting on the TNP-470-NP. In vitro, TNP-470-NP-APRPG exhibited effective inhibition of proliferation, migration and tube formation in human umbilical vein endothelial cells (HUVECs). Similar findings were observed for the retardation of tumor growth in SKOV3 ovarian cancer-bearing mice, suggesting the significant inhibition of angiogenesis and antitumor efficiency of TNP-470-NP-APRPG. Moreover, no obvious toxic drug responses were observed. Further evidence obtained from the immunohistochemical examination demonstrated that the tumor growth inhibition was closely correlated with the high rate of apoptosis among endothelial cells and the effective blockade of endothelial cell proliferation. These results demonstrate that NP-APRPG is a promising carrier for delivering TNP-470 to treat ovarian cancer and that this approach has the potential to achieve broad tumor coverage in the clinic.
authors.affiliation: Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, PR China; Shanghai Key Laboratory of Gynecologic Oncology, Shanghai 200127, PR China.
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Peifeng
authors.initials: P
authors.lastname: Liu
authors.forename: Yourong
authors.initials: Y
authors.lastname: Duan
authors.forename: Xia
authors.initials: X
authors.lastname: Yin
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Liu
authors.forename: Xinran
authors.initials: X
authors.lastname: Wang
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhou
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.forename: Lihua
authors.initials: L
authors.lastname: Qiu
authors.forename: Wen
authors.initials: W
authors.lastname: Di
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D003510:Cyclohexanes / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D009842:Oligopeptides / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D010053:Ovary / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D009842:Oligopeptides; D012717:Sesquiterpenes; C490869:alanyl-prolyl-arginyl-prolyl-glycine; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D000077609:O-(Chloroacetylcarbamoyl)fumagillol
keywords: Antiangiogenesis; Antitumor efficiency; Nanoparticles; Ovarian cancer; TNP-470