Abstract
A melittin-targeting drug carrier was successfully synthesized by the grafting of sodium alginate to an oligopeptide via an amidation method at different oligopeptide:alginate unit molar ratios. The average sizes of the oligopeptide–alginate nanoparticles formed in the presence of 1 mM CaCl2 decreased with increasing oligopeptide contents, indicating intramolecular interactions between oligopeptide-side chains. While the doxorubicin-loading efficiency on nanoparticles (0.1:1) was similar to that of alginate nanoparticles, the melittin-loading onto oligopeptide–alginate nanoparticles (0.1:1) was more than double that onto alginate nanoparticles, suggesting the specific interaction of melittin with the oligopeptide-side chain in the oligopeptide–alginate nanoparticles. While 2.5 μM free melittin caused almost no damage to Caco-2 cells, more than 80% of cells did not survive under the dose of 2.5 μM melittin-loaded oligopeptide–alginate nanoparticles. The results confirm that the derivation of an oligopeptide-side chain in alginate offers a specific binding site for melittin and effectively works in cancer chemotherapy.
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Acknowledgements
This work was financially supported by the National Taiwan University of Science and Technology, Taiwan, under Grant Number 100H451201. KW appreciates the financial support from the National Taiwan University of Science and Technology, Taiwan, for postdoctoral scholarship.
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Wattanakul, K., Imae, T., Chang, WW. et al. Oligopeptide-side chained alginate nanocarrier for melittin-targeted chemotherapy. Polym J 51, 771–780 (2019). https://doi.org/10.1038/s41428-019-0191-6
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DOI: https://doi.org/10.1038/s41428-019-0191-6
