Oligopeptide-side chained alginate nanocarrier for melittin-targeted chemotherapy

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. A melittin-targeting drug carrier was synthesized by the grafting of sodium alginate to an oligopeptide. The melittin-loading onto oligopeptide–alginate nanoparticles at 0.1:1 unit ratio was more than double that onto alginate nanoparticles, suggesting the specific interaction of melittin with the oligopeptide-side chain in the oligopeptide–alginate nanoparticles. More than 80% of Caco-2 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.