종양 치료를 위한 히알루론산 기반 포도당 감응성 나노입자

Abstract

Polymeric nanoparticles have been widely used for cancer diagnosis and therapy as they can be fabricated to enhance tumor targeting ability and reduce undesirable side effects that may occur with conventional therapeutic agents. Generally, cancer cells feature high aerobic glycolysis owing to critical damage of mitochondrial respiration and hypoxia stress in the cells. In this thesis, hyaluronate-based, glucose-responsive nanoparticles that respond to the change of glucose concentrations in cellular microenvironments were designed and prepared. Phenylboronic acid has low immunogenicity and low cytotoxicity, and was chosen as a hydrophobic moiety to be chemically conjugated to the backbone of hyaluronate via carbodiimide chemistry. Nanoparticles were prepared by self-assembly of the polymer amphiphiles in water. Various characteristics of glucose-responsive nanoparticles were examined using 1H-NMR, FT-IR, AFM, and light scattering method. Structural changes in response to glucose and other monosaccharides were also investigated using fluorescence spectroscopy. Cytotoxicity, ATP contents, lactate secretion, flow cytometric analysis, and receptor-mediated cellular uptake were also evaluated in vitro using hepatocytes. Moreover, these nanoparticles have shown targeting ability to the tumor site by enhanced permeability and retention effect as well as by receptor-mediated endocytosis. Therapeutic efficacy of nanoparticles were also confirmed using a tumor-bearing mouse model. Glucose-responsive hyaluronate-based nanoparticles exhibited excellent anti-glycolysis effect and may provide a useful means for cancer diagnosis and therapy.