Abstract
In this study, we developed facile synthesis method of multilayered polysaccharidic vesicles (hereafter termed ‘mPSVs’) using polysaccharides such as starch, hyaluronate (HA), and glycol chitosan (GC) via simple chemistry and using enzymatic reactions among polysaccharides. The enzymatic degradation of the HA shell by hyaluronidase (HYAL) enzyme contributed to accelerate the release of protein/peptide from the mPSVs. The mPSVs containing folate ligand and apoptotic cell death-inducing D-(KLAKLAK)2 peptide were effectively accumulated in in vivo KB tumor cells, primarily owing to passive tumor penetration via the enhanced permeability and retention (EPR) effect and active targeting via specific binding to folate receptors expressed on KB tumor cells. These mPSVs resulted in a significant increase in the in vivo tumor inhibition. This vesicle system is expected to exhibit great potential as an advanced platform technology for biomedical applications involving small molecular drugs with protein/gene targets.
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