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Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization.

ABSTRACT: Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders.

SUBMITTER: Lee JE

PROVIDER: S-EPMC5503670 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization.

Lee Jung Eun JE Kim Koung Li KL Kim Danbi D Yeo Yeongju Y Han Hyounkoo H Kim Myung Goo MG Kim Sun Hwa SH Kim Hyuncheol H Jeong Ji Hoon JH Suh Wonhee W

International journal of nanomedicine 20170705

Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularizatio ...[more]

PMID: 28740387

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Project description:PurposeThe S100A protein family is involved in various inflammatory processes. Two of its members, S100A4 and A13, are thought to be pro-angiogenic in tumor development. This study examines whether S100A proteins are involved in the pathogenesis of inflammation-associated corneal neovascularization (CorNV).MethodsWe used 10-0 nylon suture--(S) or chemical burn (CB)--induced CorNV models for a microarray analysis of the genome-wide expression pattern. At different time points after suturing, we conducted histopathological examinations to detect the infiltration of inflammatory cells into the corneal stroma. Representative members of the S100A family (S100A4, S100A6, S100A8, S100A9, and S100A13), pro-inflammatory cytokines (IL-1β, IL-6, transforming growth factor β1, and MIP-2), and pro-angiogenic factors (fibroblast growth factor and vascular endothelial growth factor) were detected with reverse-transcription quantitative PCR (RT-QPCR). We used immunofluorescence to monitor neutrophil or macrophage infiltration and S100A8 or S100A9 protein deposition in neovascularized corneas. Antibody-mediated neutrophil depletion or S100A8 depletion in mice was performed to evaluate the role of neutrophils and S100A proteins in suture-induced corneal neovascularization (S-CorNV).ResultsMicroarray profiling revealed that S100A4, S100A6, S100A8, S100A9, and S100A13 were upregulated in both CorNV models, with S100A8 and S100A9 manifesting the most significant changes compared to the normal animals. An RT-QPCR assay of these S100A genes and cytokine genes in the S-CorNV corneas showed that the changes were time-dependent, reaching the apex at day 5. Immunofluorescence analysis demonstrated that neutrophils and macrophages produce S100A8 and S100A9. The depletion of neutrophils beginning one day before S-CorNV induction decreased disease severity and S100A8/S100A9 deposition in the neovascularized corneas. The extent of upregulation of other detected S100A genes and pro-inflammatory or pro-angiogenic genes was also decreased by neutrophil depletion. Subconjunctival administration of S100A8 antibodies also significantly inhibited the growth of vessels and inflammation in the S-CorNV model.ConclusionsWe determined that S100A proteins are involved in the inflammatory CorNV model and that S100A8 or S100A9 in particular might be employed as targets in managing diseases involving this pathological process.

Dataset Information

Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization.

Publications

Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization.

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