Self-assembling Peptide Based Cellular Delivery of Hydrophobic Anticancer Drug
Introduction: Cancer drug delivery has limitations of delivering hydrophobic anticancer drugs and non-targeted adverse effects to normal tissues. This work explores the self-assembling peptide EAK16-II for delivery of hydrophobic anticancer drug ellipticine in human lung carcinoma A549 cells. Hyp...
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Language: | en_ca |
Published: |
2009
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Online Access: | http://hdl.handle.net/1807/30120 |
Summary: | Introduction: Cancer drug delivery has limitations of delivering hydrophobic anticancer drugs and non-targeted adverse effects to normal tissues. This work explores the self-assembling peptide EAK16-II for delivery of hydrophobic anticancer drug ellipticine in human lung carcinoma A549 cells.
Hypothesis: Self-assembling peptide based nanoparticles enhance cellular delivery of the hydrophobic anticancer drug ellipticine through an endocytotic mechanism.
Methods: EAK16-II and ellipiticine were formulated in water, and size and morphology determined using transmission electron microscopy and dynamic light scattering. The anticancer activity was evaluated by MTS assay. The cellular uptake and subcellular distribution of drug was characterized using endocytotic inhibitors and trackers.
Results: EAK16-II can form nanoparticles with ellipticine and has comparable anticancer activity to ellipticine in DMSO. Nano-formulation has enhanced drug uptake through the caveolin dependent pathway. The drug localizes to lysosome and target organelles.
Conclusion: EAK16-II forms nanoparticles with the drug and enhances cellular uptake through a caveolin-dependent endocytotic mechanism. |
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