PEG脂质体增强藻蓝蛋白亚基对乳腺癌细胞光毒性的研究

藻蓝蛋白亚基(PCS)是一种低毒并具良好荧光活性的光敏剂.为了增加PCS对乳腺癌细胞的PDT疗效,制备了聚乙二醇修饰的藻蓝蛋白亚基脂质体(PEG-PCS-lip).该脂质体的平均粒径为(136.3±7.6)nm,包封率达到52.1%.在浓度为100mg/L时,PEG-PCS-lip组在MCF-7细胞中的转染率在5h达到(29.1±1.2)%,是PCS-lip组的1.5倍,PCS组的3.1倍.PEG-PCS-lip光动力作用半致死剂量对MCF-7及MA-782细胞分别为(65.4±2.47)mg/L及(70.5±2.95)mg/L.用100mg/L的PEG-PCS-lip进行PDT处理后凋亡率达到了28.5%.与PCS相比,PEG-PCS-lip在血液和肿瘤中比在其他组织中聚集的浓度更高、时间更久,并在注射10h后达到峰值.PCS-PEG-lip-PDT处理组(每千克体重静脉给药10mg,照射剂量为150J/cm2)的肿瘤生长率下降至8.4%,而同时对照组肿瘤大小约增加了两倍.HE组织切片染色和透射电镜观察发现PEG-PCS-lip-PDT组的肿瘤细胞经历了凋亡和坏死.这些数据都表明,相比于PCS和PCS-li...

The phototoxicity of phycocyanin subunit was enhanced by PEGylated liposome against breast cancer

Due to good fluorescence character, better PDT effect and weak phototoxicity,phycocyanin subunit (PCS) is an attractive option for improving the selectivity of photosensitizer.In order to enhance the efficiency of PCS based PDT on breast cancer cells, polyethyleneglycol modified phycocyanin subunit liposome (PEG-PCS-lip) was prepared by PEGylated modification.The particle size of each PEG-PCS-Iip was (136.3± 7.6)nm and the entrapment ratio reached (52. 1±4.5)%. At the concentration of 100 mg/L, the transfection rate in MCF-7 cells of the PEG-PCS-lip group was markedly increased to a higher level of (29. 1± 1.2)% by 1.5-fold of that in the PCS-Iip group and 3. 1-fold of that in the PCS group at 5 h. By using PEGylated liposome carrier, the half lethal dose of PEG-PCS-Iip-PDT group reached (65.4± 2. 47)mg/L in MCF-7 ceils and (70. 5±2.95)mg/L in MA-782 cells, which was much lower than that of PCS-PDT group and PCS-lip-PDT group (P＜0. 001). The apoptotic rate reached (28.5±3.5)Z% with PDT treatment at the concentration of 100 mg/L PEG-PCS-lip. Compared to PCS, PEG-PCS-lip concentrated more and stayed longer in tumor and blood than other tissues and reached a peak at 10 h after injection. The tumor growth rate of PEG-PCS-lip-PDT group decreased to 8. 4%, while the tumor size of the control group tripled. Observation by HE staining and transmission electron microscopy (TEM) indicate that tumor cells of the PEG-PCS-lip-PDT group were undergoing apoptosis and necrosis. Our data suggest that PEGylated liposome carrier increases the PCS accumulation in tumor cells and enhances its PDT effect on breast cancer compared to free PCS.