Synthesis, characterization, and intracellular delivery of reducible heparin nanogels for apoptotic cell death

Ki Hyun Bae, Hyejung Mok, Tae Gwan Park

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

Reducible heparin nanogels cross-linked with disulfide linkages were developed for efficient cellular uptake of therapeutic heparin to induce apoptotic cell death. The heparin nanogels were synthesized by forming nanocomplexes between thiolated heparin and poly(ethylene glycol) in a selected organic solvent, and subsequently producing intermolecular disulfide bonds between thiolated heparin molecules by ultrasonication. The resultant heparin nanogels had a stable structure with an average diameter of 248.7 ± 26.8 nm in aqueous solution. However, they rapidly disintegrated and released free heparin molecules under reductive environments, such as intracellular cytosol, through the cleavage of disulfide cross-links within their network structure. Confocal laser scanning microscopy and flow cytometric analysis revealed that these heparin nanogels significantly inhibited proliferation of mouse melanoma cells by inducing caspase-mediated apoptotic cell death. The present study suggested that the reducible heparin nanogels exhibiting a remarkable apoptotic activity could be potentially applied for cancer cell targeted delivery when combined with various therapeutic and diagnostic agents.

Original languageEnglish
Pages (from-to)3376-3383
Number of pages8
JournalBiomaterials
Volume29
Issue number23
DOIs
StatePublished - Aug 2008
Externally publishedYes

Funding

This research was supported by the Ministry of Health and Welfare, and the National Research Laboratory program from the Ministry of Science and Technology, Republic of Korea.

FundersFunder number
Ministry of Health and Welfare
Ministry of Science and Technology

    Keywords

    • Apoptosis
    • Disulfide
    • Drug delivery system
    • Heparin
    • Nanogel

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