earticle

영어

Photodynamic therapy (PDT), which employs photosensitizers (PSs), a light source with appropriate wavelength, and oxygen molecules, has potential for the treatment of various tumors and non-oncological diseases due to its high efficiency in directly producing cellular death, vascular shutdown, and immune activation. For the past decade, many PSs were developed with improved optical and chemical properties. However, some weak points still remain such as low solubility and low tumor specificity by hydrophobic PSs. So, many PDT studies based on soluble polysaccharide carriers such as PSs conjugated polysaccharide nanocarrier and PSs loaded nanocarrier have been carried out in order to improve the water solubility and target specificity of PSs. In case of our group, we prepared the polysaccharide based nanocarrier system composed of cancer cell target-moiety-labeled polysaccharide-graft PS by a dialysis method to improve their targeting efficiency and water solubility. The synthesis was confirmed by 1H NMR spectroscopy, and degree of substitution was determined by UV-spectrophotometery. The size of spherical nanogels was approximately 170 nm, and its photocytotoxicity was studied by an XTT assay. While the PS grafted nanocarrier circulated in the blood, the nanocarrier’s photoactivity may be suppressed by a self-quenching effect between PS molecules in the PS grafted nanocarrier system, similar to the fluorescence resonance energy transfer (FRET) effect. Because the PS grafted nanocarrier system is thought to be internalized into cancer cells following tissue penetration, its photoactivity may be restored without the FRET effect by cleavage of its ester bonds through enzymatic attack in the extracellular matrix and cellular compartments such as lysosomes. The PS grafted nanocarrier system showed a self-quenching activity in the aqueous environment, and has the capacity of tumor tissue targeting by nano-size induced EPR. After accumulation of the PS grafted nanocarrier system in tumors, the fluorescence signals will be gradually enhanced by the release of the PS from broken PS grafted nanocarrier caused by cleavable ester linkage. The phototoxicity effects in the cells by the irradiation of external light resulted in generation of singlet oxygen, at the same time when the near-infrared fluorescence molecular imaging can be detected.