摘要
以表面接枝聚乙二醇链的聚酰胺胺树枝状聚合物(PEG-PAMAM)为纳米载体,在其内部空腔包覆金纳米粒子,在金纳米粒子表面连接硫辛酸改性的阿霉素(LA-DOX),从而间接实现了抗癌药物在PEGPAMAM内的高效负载.同时,LA-DOX中的酰腙键提供pH响应性,实现了药物的pH响应性释放.紫外-可见(UV-Vis)光谱表明,包覆金纳米粒子的PEG-PAMAM纳米载体对LA-DOX的负载能力显著增强.体外细胞实验表明,负载LA-DOX的树枝状聚合物-金纳米粒子复合药物载体具有较强的抗肿瘤能力.
Dendrimer-gold nanoparticle composites were prepared based on poly(ethylene glycol) modified dendrimer(PEG-PAMAM). Gold nanoparticles internal provided an efficient platform for lipoic acid functionalized DoxorubicinLA-DOX linking,leading to the high loading efficiency of anticancer drugs DOX. Meanwhile the hydrazine linker in LA-DOX realized pH sensitive release for nanocarrier. Verified by UV-Vis spectra,the loading efficiency of LA-DOX in dendrimer-gold nanoparticle nanocomposite was improved. Cell Experiment indicated excellent cytotoxicity of dendrimer-gold nanoparticle composite against Hela cells.
引文
[1] Hu Q.,Studies on the Construction and in vitro Anti-cancer Efficiency of Multifunctional PAMAM-DOX Conjugates Drug Delivery System,Soochow University,Suzhou,2013(胡青.多功能PAMAM聚合物递药系统的构建及体外抗肿瘤研究,苏州:苏州大学,2013)
[2] Sun R.,Zhu W.,Liu Y. Q.,Journal of Pharmaceutical Research,2014,33,249—252(孙蕊,朱琰,刘玉琴.药学研究,2014,5,249—252)
[3] Hu H. X.,Wang X. Q.,Zhang H.,Zhang Q.,Journal of Pharmaceutical Sciences,2015,10,1232—1239(胡宏祥,王学清,张华,张强.药学学报,2015,50,1232—1239)
[4] Mintzer M. A.,Grinstaff M. W.,Chem. Soc. Rev.,2010,40,173—190
[5] Tomalia D. A.,Soft Matter,2010,6,456—474
[6] Astruc D.,Boisselier E.,Ornelas C.,Chem. Rev.,2010,110,1857—1959
[7] Haensler J.,Francis S. C. Jr.,Bioconjugate Chem.,1993,4,372—379
[8] Jevprasesphant R.,Penny J.,Jalal R.,Attwood D.,Mckeown N. B.,D’Emanuele A.,Int. J. Pharm.,2003,252,263—266
[9] Malik N.,Wiwattanapatapee R.,Klopsch R.,Lorenz K.,Frey H.,Weener J. W.,J. Controlled Release,2000,65,133—148
[10] Kolhatkar R. B.,Kitchens K. M.,Swaan P. W.,Ghandehari H.,Bioconjugate Chem.,2007,18,2054—2060
[11] Majoros I. J.,Myc A.,Thomas T.,Mehta C. B.,Baker J. R.,Biomacromolecules,2006,7,572—579
[12] Shi X.,Wang S.,Sun H.,Baker J. R.,Soft Matter,2007,3,71—74
[13] Cheng Y.,Zhao L.,Li Y.,Xu T.,Chem. Soc. Rev.,2011,40,2673—2703
[14] Kojima C.,Kono K.,Maruyama K.,Takagishi T.,Bioconjugate Chem.,2000,11,910—917
[15] Kojima C.,Toi Y.,Harada A.,Kono K.,Bioconjugate Chem.,2007,18,663—670
[16] Wang X.,Cai X.,Hu J.,Shao N.,Wang F.,Zhang Q.,Xiao J. R.,Cheng Y. Y.,J. Am. Chem. Soc.,2013,135,9805—9810
[17] Figueroa E. R.,Lin A. Y.,Yan J.,Luo L.,Foster A. E.,Drezek R. A.,Biomaterials,2014,35,1725—1734
[18] Wei Y.,Li Y.,Zhang N.,Shi G.,Jin L.,Ultrason Sonochem,2010,17,17—20
[19] Li X. J.,Takashima M.,Yuba E.,Harada A.,Kono K.,Biomaterials,2014,35,6576—6584
[20] HrubM.,Konák C.,Ulbrich K.,J. Controlled Release,2005,103,137—148
[21] Ma Y.,Fan X.,Li L.,Carbohydr. Polym.,2016,137,19—29
[22] Kojima C.,Kono K.,Maruyama K.,Takagishi T.,Bioconjugate Chem.,2000,11,910—917
[23] Kono K.,Takeda K.,Li X.,Yuba E.,Harada A.,Ozaki T.,Mori S.,RSC. Adv.,2014,4,27811—27819
[24] Yu P. L.,Li S. T.,Ye L.,Yang H.,Wang C. X.,Chinese J. Biomed. Eng.,2007,26,921—925(余沛霖,李慎涛,叶玲,杨华,王丛霞.中国生物医学工程学报,2007,26,921—925)