근적외선 감지 상향변환 나노입자를 이용한 표적형 광역학 암치료 연구

Abstract

Photodynamic therapy (PDT) can cause cancer tissue death by using a light source and molecular oxygen. However, despite its usefulness, tissue permeability is limited during light irradiation. Recently, photosensitizers (PS) that respond to near-infrared (NIR) light have been developed to overcome this problem; still, the therapeutic efficacy is low due to the lack of target specificity of cancer cells. To solve this problem, PDT was proposed using upconversion nanoparticles (UCNPs) that absorb near NIR rays and emit visible light and a recombinant photosensitizing protein that specifically targets cancer cells. The NIR-sensitizing UCNPs consisted of a green-emitting core/shell UCNP doped with lanthanide ions, a red fluorescent protein variant (KillerRed; KR), and a cancer cell-targeting lead peptide (LP); they were denoted as UCNP-KR-LPs. In the regime of UCNPs that effectively convert NIR light into green light emission, the KRs generated superoxide anion radicals as the reactive oxygen species (ROS) upon green light irradiation, and the LP fused to the KR conferred target specificity to cancer cells via integrin beta 1 (ITGB1)-mediated cell adhesion. As a result, the UCNP-KR-LPs caused rapid death of the cancer cell lines (MCF-7, MDA-MB-231 and U-87MG) overexpressed with ITGB1, but not in the cell line (SK-BR-3) with reduced ITGB1 expression or non-invasive normal mammary cell line (MCF-10A). When comparing cancer cell death effects in visible and NIR light using porcine skin layers as a model to confirm tissue penetration, cell death was observed up to a depth of 2 and 10 mm, respectively. In conclusion, the UCNP-KR-LPs developed in this study can be applied as a PDT to various cancer tissues and has demonstrated a highly targeted therapeutic effect.