Development of pH-responsive starch-glycol chitosan nanogels for proapoptotic (KLAKLAK)(2) peptide delivery

Abstract

In this study, we report pH-responsive polysaccharidic nanogels for cytosolic peptide delivery. We conjugated starch to water-soluble glycol chitosan and pH-responsive 3-diethylaminopropylamine (starch-(glycol chitosan-3-diethylaminopropylamine)). Starch-(glycol chitosan-3-diethylaminopropylamine) self-organizes in aqueous solution, with the glycol chitosan blocks on the hydrophilic outer shell and starch and 3-diethylaminopropylamine blocks in the hydrogel inner core. The experimental results demonstrated that the protonation of 3-diethylaminopropylamine at pH 6.0 (endosomal pH) allowed for accelerated release of the encapsulated D-(KLAKLAK)(2) proapoptotic peptide from the nanogels as a result of electrostatic repulsion between D-(KLAKLAK)(2) and 3-diethylaminopropylamine. A hemolysis test using red blood cell membranes (as an endosomal membrane model) revealed the excellent endosomolytic activity of these nanogels, which likely stems from the proton-sponge effect of 3-diethylaminopropylamine at pH 6.0. As a result, these nanogels resulted in increased KB tumor cell ablation.