Intracellular Delivery of Heparin Complexed with Chitosan-g-Poly(Ethylene Glycol) for Inducing Apoptosis

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Chitosan-g-PEG/heparin polyelectrolyte complex micelles were prepared for inducing apoptotic death of cancer cells. The cytotoxicity of polyelectrolyte complex micelles was evaluated by examining the growth inhibition of mouse melanoma B16F10 cells. Cellular uptake and apoptosis-inducing effect were investigated by confocal laser scanning microscopy and flow cytometric analysis, respectively. The prepared polyelectrolyte complex micelles had a spherical shape with an average diameter of 162.8 +/- 18.9 nm. They were highly stable and well dispersed even in the presence of serum due to the presence of hydrophilic PEG shell layer surrounding the micelles. Moreover, they exhibited significantly higher cytotoxic activity against B16F10 cells compared to heparin or chitosan-g-PEG at the same concentration. The polyelectrolyte complex micelles were internalized by cancer cells to a greater extent than free heparin alone, indicating that the dramatic cell death was attributed to the increased cellular uptake of heparin. The internalized heparin was shown to induce apoptotic death of the cancer cells via a caspase-dependent pathway. Nanosized and stable chitosan-g-PEG/heparin polyelectrolyte complex micelles were produced by a self-assembly process. The polyelectrolyte complex micelles facilitated the intracellular delivery of heparin, triggered the caspase activation, and consequently promoted apoptotic death of cancer cells.
Publisher
SPRINGER/PLENUM PUBLISHERS
Issue Date
2009-01
Language
English
Article Type
Article
Keywords

CELL-DEATH; CHITOSAN; CANCER; GENE; CARRIERS; NANOPARTICLE; METASTASIS; PEGYLATION; MICELLES

Citation

PHARMACEUTICAL RESEARCH, v.26, no.1, pp.93 - 100

ISSN
0724-8741
DOI
10.1007/s11095-008-9713-1
URI
http://hdl.handle.net/10203/13167
Appears in Collection
BS-Journal Papers(저널논문)
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