中国科学技术大学学报
中國科學技術大學學報
중국과학기술대학학보
JOURNAL OF UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA
2011年
1期
35-44
,共10页
周桃%黄蓓%左漫漫%郭瑞勇%王永中%牛建峰
週桃%黃蓓%左漫漫%郭瑞勇%王永中%牛建峰
주도%황배%좌만만%곽서용%왕영중%우건봉
藻蓝蛋白亚基%PEG脂质体%光动力学疗法%乳腺癌
藻藍蛋白亞基%PEG脂質體%光動力學療法%乳腺癌
조람단백아기%PEG지질체%광동역학요법%유선암
phycocyanin subunit%liposome%photodynamic therapy%breast cancer
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-Iip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(65.45±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-Iip-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-Iip-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-Iip,PEG脂质体能够增强PCS在肿瘤细胞聚集的靶向性,提高PDT疗效.
藻藍蛋白亞基(PCS)是一種低毒併具良好熒光活性的光敏劑.為瞭增加PCS對乳腺癌細胞的PDT療效,製備瞭聚乙二醇脩飾的藻藍蛋白亞基脂質體(PEG-PCS-lip).該脂質體的平均粒徑為(136.3±7.6)nm,包封率達到52.1%.在濃度為100mg/L時,PEG-PCS-Iip組在MCF-7細胞中的轉染率在5h達到(29.1±1.2)%,是PCS-lip組的1.5倍,PCS組的3.1倍.PEG-PCS-lip光動力作用半緻死劑量對MCF-7及MA-782細胞分彆為(65.45±2.47)mg/L及(70.5±2.95)mg/L.用100mg/L的PEG-PCS-lip進行PDT處理後凋亡率達到瞭28.5%.與PCS相比,PEG-PCS-lip在血液和腫瘤中比在其他組織中聚集的濃度更高、時間更久,併在註射10h後達到峰值.PCS-PEG-Iip-PDT處理組(每韆剋體重靜脈給藥10mg,照射劑量為150J/cm2)的腫瘤生長率下降至8.4%,而同時對照組腫瘤大小約增加瞭兩倍.HE組織切片染色和透射電鏡觀察髮現PEG-PCS-Iip-PDT組的腫瘤細胞經歷瞭凋亡和壞死.這些數據都錶明,相比于PCS和PCS-Iip,PEG脂質體能夠增彊PCS在腫瘤細胞聚集的靶嚮性,提高PDT療效.
조람단백아기(PCS)시일충저독병구량호형광활성적광민제.위료증가PCS대유선암세포적PDT료효,제비료취을이순수식적조람단백아기지질체(PEG-PCS-lip).해지질체적평균립경위(136.3±7.6)nm,포봉솔체도52.1%.재농도위100mg/L시,PEG-PCS-Iip조재MCF-7세포중적전염솔재5h체도(29.1±1.2)%,시PCS-lip조적1.5배,PCS조적3.1배.PEG-PCS-lip광동력작용반치사제량대MCF-7급MA-782세포분별위(65.45±2.47)mg/L급(70.5±2.95)mg/L.용100mg/L적PEG-PCS-lip진행PDT처리후조망솔체도료28.5%.여PCS상비,PEG-PCS-lip재혈액화종류중비재기타조직중취집적농도경고、시간경구,병재주사10h후체도봉치.PCS-PEG-Iip-PDT처리조(매천극체중정맥급약10mg,조사제량위150J/cm2)적종류생장솔하강지8.4%,이동시대조조종류대소약증가료량배.HE조직절편염색화투사전경관찰발현PEG-PCS-Iip-PDT조적종류세포경력료조망화배사.저사수거도표명,상비우PCS화PCS-Iip,PEG지질체능구증강PCS재종류세포취집적파향성,제고PDT료효.
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.