Nanoparticle-induced tight-junction opening for the transport of an anti-angiogenic sulfated polysaccharide across Caco-2 cell monolayers

Shu Huei Yu, Deh Wei Tang, Hao Ying Hsieh, Wen Shin Wu, Bo Xian Lin, Er-Tuan Chuang, Hsing Wen Sung, Fwu Long Mi

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

Fucoidan has the ability to inhibit angiogenesis by human umbilical vein endothelial cells (HUVECs). However, a major clinical limitation is its poor oral availability because fucoidan is a hydrophilic macromolecule. In this study, an oversulfation reaction of fucoidan has been performed to enhance its anti-angiogenic activities. The synthesized, oversulfated fucoidan (OFD) was characterized by Fourier transform infrared spectroscopy. The oversulfate content of OFD was estimated to be 41.7% by using a BaCl2 gelatin method. Nanoparticles (NPs) composed of chitosan (CS) and OFD were prepared by a polycation-polyanion complex method. The mean particle sizes of prepared CS/OFD NPs were in the range of 172-265 nm with a negative or positive surface charge, depending on the relative concentrations of CS to OFD used. The self-assembled NPs with pH-sensitive characteristics could be used as a pH-switched nanocarrier for oral delivery of the antiangiogenic macromolecule, OFD, in response to simulated gastrointestinal (GI) tract media. Evaluation of test NPs in enhancing the intestinal paracellular transport of OFD suggested that the NPs with a positive surface charge could transiently open the tight junctions between Caco-2 cells and thus increase the paracellular permeability. Tight-junction opening and restoration were examined by monitoring the redistribution of ZO-1 tight-junction proteins using confocal laser scanning microscopy (CLSM). The transported OFD significantly inhibits the tube formation of HUVECs via competitive binding of OFD and basic fibroblast growth factor (bFGF) to bFGF receptors (bFGFRs).

Original languageEnglish
Pages (from-to)7449-7459
Number of pages11
JournalActa Biomaterialia
Volume9
Issue number7
DOIs
Publication statusPublished - Jul 2013

Keywords

  • Chitosan
  • Fucoidan
  • Nanoparticles
  • Oral delivery

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biotechnology
  • Biochemistry
  • Molecular Biology

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