Photodynamic Therapy with Glycoconjugated Chlorin Photosensitizer
Photodynamic Therapy with Glycoconjugated Chlorin Photosensitizer
复制标题
糖共轭二氢卟酚光敏剂的光动力疗法
DOI：
10.1142/s1088424613500065
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发表时间：
2013
影响因子：
1.5
通讯作者：
A. Morita
中科院分区：
文献类型：
--
作者：
S. Sakuma;E. Otake;K. Torii;M. Nakamura;A. Maeda;R. Tujii;H. Akashi;H. Ohi;S. Yano;A. Morita
光动力疗法（PDT）能有效诱导肿瘤细胞凋亡，但常用光敏剂如天冬氨酸氯（NPe6）的肿瘤选择性和光敏性不够。癌细胞吞噬葡萄糖的效率是正常细胞的3 ~ 20倍；因此，我们研究了糖缀合是否能提高光敏剂的肿瘤定位能力。HaCaT细胞用H2TFPC（未偶联氯）、H2TFPC- sglc（糖偶联氯）或NPe6孵育，然后用633 nm LED光（16 J.cm-2）照射。1 μM H2TFPC- sglc作用24 h， annexinV+细胞凋亡率为74.5%，显著高于H2TFPC（2.9%）和NPe6（0.3%）。根据IC50，在所有检测的细胞系中，PDT与H2TFPC- sglc比NPe6或H2TFPC更有效地诱导肿瘤细胞死亡。在辐照过程中加入叠氮化钠（单线态氧猝灭剂）可显著抑制PDT诱导的COLO679细胞凋亡（-0.4±0.3%→119±44%），而与氧化氘（单线态氧增强剂）共孵育可增强PDT（72±19→27±5%）。共聚焦显微镜显示H2TFPC-SGlc在溶酶体和高尔基体中积累，而不在线粒体和内质网中积累。在荷瘤小鼠中，瘤内注射H2TFPC-SGlc (10-8mol或10-9mol)， 4 h后用633 nm LED光（150 J.cm-2）连续照射13天（10-8mol），控制肿瘤生长。因此，PDT与H2TFPC-SGlc通过单线态氧诱导有效地诱导肿瘤细胞凋亡。
Photodynamic therapy (PDT) effectively induces tumor cell apoptosis, but the tumor selectivity and photosensitivity of common photosensitizers, such as aspartyl chlorin (NPe6), are not sufficient. Cancer cells phagocytose glucose 3 to 20 times more efficiently than normal cells; therefore, we examined whether glycoconjugation improves photosensitizer tumor-localizability. HaCaT cells were incubated with H2TFPC (unconjugated chlorin), H2TFPC-SGlc (glycoconjugated chlorin), or NPe6, followed by irradiation with 633 nm LED light (16 J.cm-2). PDT with 1 μM H2TFPC-SGlc for 24 h induced significantly more apoptosis (annexinV+cells: 74.5%) than PDT with either H2TFPC (2.9%) or NPe6 (0.3%). Based on the IC50, PDT with H2TFPC-SGlc induced tumor cell death more efficiently than NPe6 or H2TFPC in all cell lines examined. The addition of sodium azide, a singlet oxygen quencher, during irradiation significantly suppressed PDT-induced apoptosis in COLO679 cells (-0.4 ± 0.3% → 119 ± 44%), whereas coincubation with deuterium oxide, a singlet oxygen enhancer, enhanced PDT (72 ± 19 → 27 ± 5%). Confocal microscopy revealed that H2TFPC-SGlc accumulated in lysosomes and Golgi bodies, but not in mitochondria or endoplasmic reticulum. In melanoma-bearing mice, intratumoral injection of H2TFPC-SGlc (10-8mol or 10-9mol), followed 4 h later by irradiation with 633 nm LED light (150 J.cm-2) controlled tumor growth for 13 consecutive days (10-8mol). Thus, PDT with H2TFPC-SGlc effectively induces apoptosis in tumor cellsviasinglet oxygen induction.