负载芳基苄醚树枝形酞菁锌聚合物纳米粒子的合成及其离体光动力活性  

Synthesis and Characterization of Polyion Complex Micelle Loaded with Zinc(Ⅱ) Phthalocyanine Bearing Poly(aryl benzyl ether) Dendrimer

作　　者：阙寿林[1] 彭亦如[1] 张宏[1] 陈莉莉[1] 黄丽珊[1] 刘建生[1] 陈奎治[1] 吴松一[2] 

机构地区：[1]福建师范大学化学与材料学院福建省高分子材料重点实验室,福州350007 [2]福建医科大学附属第一医院,福州350005

出　　处：《化学学报》2011年第6期731-738,共8页Acta Chimica Sinica

基　　金：国家自然科学基金(No.20604007);福建省科技厅重点项目(No.2007J0013);福建省自然科学基金(No.2008J0078);卫生部科学研究基金(No.WKJ2008-2-61)资助项目

摘　　要：首先将对氰基溴化苄与3,5-二羟基苯甲醇通过Frétchet反应合成芳基苄醚树枝分子3,5-[二-(4'-氰基苯甲氧基)]苯甲醇(1),1与4-硝基邻苯二甲腈合成前驱物4-{3',5'-[二-(4''-氰基苯甲氧基)]}苯甲氧基邻苯二甲腈(3),然后3在乙酸锌,1,8-二氮杂二环(5,4,0)-7-十一烯(DBU)和正戊醇存在下合成以氰基为端基的芳基苄醚树形酞菁锌配合物四-{3,5-[二-(4'-氰基苯甲氧基)-苯甲氧基]}锌酞菁(4),最后4在氢氧化钠中水解制备以羧基为端基的芳基苄醚树形酞菁锌四-{3,5-[二-(4'-羧基苯甲氧基)-苯甲氧基]}锌酞菁(5).采用元素分析、ⅠR,1H NMR,ESⅠ-MS和MALDⅠ-TOF-MS对上述化合物的结构进行了表征.带有负电荷的5与两嵌段共聚物聚乙二醇单甲醚-聚L-赖氨酸(PEG-b-PLL)(6)通过静电作用自组装成负载5的聚合物纳米粒子(5/m).AFM和TEM表明5/m为直径约为100 nm的核壳结构纳米粒子.通过紫外光谱和荧光光谱法研究了5和5/m的光物理性质:5包裹入聚合物胶束后,5/m的Q带最大吸收峰强度增加,位置红移,荧光强度增加,荧光寿命减少.不同孵育时间HUVEC细胞(人体静脉内皮细胞)的5和5/m的药代动力学和MTT法研究表明:与自由酞菁5相比,5/m摄取率增加,提前1 h达到最大浓度而且细胞抑制率也大大增加.3,5-Di-（4＇-cyanobenzyloxy）benzyl alcohol（1） was synthesized by reaction of 3,5-di-hydroxybenzyl alcohol with 4-cyanobenzyl bromide.4-（3＇,5＇-hydroxybenzyloxy）phthalonitrile（3） was obtained by reacation of 1 with 4-nitrophthalonitrile in DMF.Tetra-[3,5-di-（4＇-cyanobenzyloxy）benzyloxy] zinc（II） phthalocyanine（4） was obtained by condensation of 3 in the presence of n-pentanol,acetate zinc（II） and DBU.The corresponding hydrophilic complexes tetra-[3,5-di-（4＇-carboxylicbenzyloxy）benzyloxy] zinc phthalocyanine（5） was obtained by hydrolyzation of 4 in NaOH.The structures of above compounds were characterized by elemental analysis,IR,1H NMR,ESI-MS,MALDI-TOF-MS,and UV/Vis.A polyion com-plex micelle system 5/m,which was formed via an electronic interaction of anionic dendrimer phthalocya-nine 5 and positively poly（L-lysine） segment of poly（ethylene glycol）-poly（L-lysine） block copolymer（PEG-b-PLL）.The morphology and photophysical properties of 5/m was investigated by AFM,TEM,UV/Vis and fluorescence spectroscopy methods.The 5/m formed a core-shell-type nanoparticle with di-ameter ca.100 nm.Electrostatic assembly of 5/m resulted in a red-shift and higher intensity of the Q band,fluorescence intensity and singlet excited life compared with free 5.The time-dependence uptake amount of 5 and 5/m in HUVEC（human umbilical vein endothelial cell） cells showed that the uptake amount of 5/m was significantly increased and reached peak value by ahead of 1 h compared with 5.The in vitro photody-namic therapy efficiency of 5 and 5/m were evaluated by MTT method,and the results indicated that the photodynamic therapy efficacy of 5/m was enhanced when the polymeric nanoparticles was loaded with dendritic phthalocyanine 5.

关 键 词：芳基苄醚树枝酞菁锌 聚乙二醇单甲醚-聚L-赖氨酸 聚合物纳米粒子 静电自组装 合成 表征 

分 类 号：O627.23[理学—有机化学]