Penjweini Rozhin, Smisdom Nick, Deville Sarah, Ameloot Marcel
Biomedical Research Institute, Hasselt University, Agoralaan Building C, 3590 Diepenbeek, Belgium.
Biomedical Research Institute, Hasselt University, Agoralaan Building C, 3590 Diepenbeek, Belgium; Flemish Institute For Technological Research, Environmental Risk and Health Unit, Boeretang 200, 2400 Mol, Belgium.
Biochim Biophys Acta. 2014 May;1843(5):855-65. doi: 10.1016/j.bbamcr.2014.01.016. Epub 2014 Jan 27.
PVP-Hypericin (PVP: polyvinylpyrrolidone) is a potent anti-cancer photosensitizer for photodynamic diagnosis (PDD) and therapy (PDT). However, cellular targets and mechanisms involved in the cancer-selectivity of the photosensitizer are not yet fully understood. This paper gives new insights into the differential transport and localization of PVP-Hypericin in cancer and normal cells which are essential to unravel the mechanisms of action and cancer-selectivity. Temporal (TICS) and spatiotemporal (STICS) image correlation spectroscopy are used for the assessment of PVP-Hypericin diffusion and/or velocity in the case of concerted flow in human cervical epithelial HeLa and human lung carcinoma A549 cells, as well as in human primary dendritic cells (DC) and human peripheral blood mononuclear cells (PBMC). Spatiotemporal image cross-correlation spectroscopy (STICCS) based on organelle specific fluorescent labeling is employed to study the accumulation of the photosensitizer in nucleus, mitochondria, early-endosomes and lysosomes of the cells and to assess the dynamics of co-migrating molecules. Whereas STICS and TICS did not show a remarkable difference between the dynamics of PVP-Hypericin in HeLa, A549 and DC cells, a significantly different diffusion rate of the photosensitizer was measured in PBMC. STICCS detected a stationary accumulation of PVP-Hypericin within the nucleus, mitochondria, early endosomes and lysosomes of HeLa and A549 cells. However, significant flow due to the directed motion of the organelles was detected. In contrast, no accumulation in the nucleus and mitochondria of DC and PBMC could be monitored.
聚乙烯吡咯烷酮 - 金丝桃素（PVP：聚乙烯吡咯烷酮）是一种用于光动力诊断（PDD）和治疗（PDT）的强效抗癌光敏剂。然而，这种光敏剂在癌症选择性方面涉及的细胞靶点和机制尚未完全明确。本文对PVP - 金丝桃素在癌细胞和正常细胞中的差异转运和定位提供了新的见解，这对于阐明其作用机制和癌症选择性至关重要。在人宫颈上皮HeLa细胞、人肺癌A549细胞、人原代树突状细胞（DC）和人外周血单核细胞（PBMC）中存在协同流动的情况下，采用时间（TICS）和时空（STICS）图像相关光谱法来评估PVP - 金丝桃素的扩散和/或速度。基于细胞器特异性荧光标记的时空图像互相关光谱法（STICCS）用于研究光敏剂在细胞的细胞核、线粒体、早期内体和溶酶体中的积累，并评估共同迁移分子的动力学。虽然STICS和TICS在HeLa、A549和DC细胞中未显示出PVP - 金丝桃素动力学的显著差异，但在PBMC中测得光敏剂的扩散速率有显著差异。STICCS检测到PVP - 金丝桃素在HeLa和A549细胞的细胞核、线粒体、早期内体和溶酶体中存在稳定积累。然而，检测到由于细胞器的定向运动导致的显著流动。相比之下，在DC和PBMC的细胞核和线粒体中未监测到积累。
