目的 制备肝素化磁介孔硅纳米粒,并负载多柔比星,考察该载药系统的体外释药及抗癌活性。方法 用相转移法和溶胶-凝胶法合成单分散核/壳结构的磁介孔硅纳米粒(MMSNs),以共价结合的方法合成肝素化磁介孔硅纳米粒,然后进行药物在肝素化磁介孔硅纳米粒上的负载与体外释放实验、肝素化磁介孔硅纳米粒的细胞摄入实验及肝素化磁介孔硅纳米粒负载多柔比星的体外细胞学实验。结果 肝素化磁介孔硅纳米粒能够明显延缓多柔比星的释放,能够被肝癌细胞HepG2摄入、对HepG2细胞具有明显的杀伤作用、对碱性成纤维细胞生长因子诱导的HepG2细胞增殖具有明显的抑制作用。结论 肝素化磁介孔硅纳米粒作为药物载体在传递抗肿瘤药物方面具有潜在的应用前景。
Abstract
OBJECTIVE To prepare doxorubicin-loased heparinized magnetic mesoporous silica nanoparticles (MMSNs-HP) and investigate their drug release profile and anticancer activity in vitro. METHODS Amino-modified MMSNs was synthesized by combining phase transfer method with sol-gel method firstly. Then heparin was conjugated with the above nanoparticles via carbodiimide chemistry to form MMSNs-HP. Finally, the following experiments were performed, such as loading/release of doxorubicin into/from MMSNs-HP in vitro, cellular uptake of MMSNs-HP by hepatoma cell HepG2 and cell cytotoxicity of doxorubicin-loaded MMSNs-HP. RESULTS MMSNs-HP was able to delay the release of doxorubicin significantly, penetrate into tumor cells, kill HepG2 cell, and inhibit the proliferation of HepG2 cells induced by basic fibroblast HepG2 cells (bFGF). CONCLUSION MMSNs-HP is a potential drug carrier for the delivery of antitumor drugs.
关键词
肝素化 /
磁介孔硅纳米粒 /
多柔比星 /
肝癌细胞
{{custom_keyword}} /
Key words
heparin /
mesoporous silica /
doxorubicin /
HepG2 cell
{{custom_keyword}} /
中图分类号：
O482.54
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] ZHUANG Y,LIU X L. Anthracycline cardiotoxicity and its preventive measures[J]. Anti-tumor Pharm(肿瘤药学),2011,1(4):322-326.
[2] MA L. 83 Cases of Cardiac toxicity of doxorubicin ECG analysis [J]. J Zhenjiang Med Coll(镇江医学院学报),2001,11(2):236-237.
[3] LIU J,XU W H,JIN C H,et al.Study on preparation of adriamycin-loaded PLGA nanoparticles in vitro[J]. Prog Mod Biomed(现代生物医学进展),2010,10(24):4661-4663.
[4] CHEN L N,WANG Y,ZHU Y, et al.Stimulus-responsive polyplexes with drug and gene co-delivery[J]. Chem J Chin Univ(高等学校化学学报), 2013,3(34):720-725.
[5] LV W L, WEI S L , ZHANG Q, et al.Comparison of the antitumour activity betweens tealth liposomal doxorubicin and regular liposomal doxorubicin[J]. Chin Pharm J(中国药学杂志),2000,35(10):670-672.
[6] WANG S N,DENG Y H,WU H B, et al.Asses sment of the Targetabil ity of galactosylated liposomes to liver in mice[J]. Chin Pharm J(中国药学杂志),2006,41(14):1076-1078.
[7] KIM J, KIM H S, LEE N, et al. Multifunctional uniform nanoparticles composed of a magnetite nanocrystal core and a mesoporous silica shell for magnetic resonance and fluorescence imaging and for drug delivery[J]. Angew Chem Int Ed, 2008, 47(44):8438-8441.
[8] GIRI S, TREWYN B G, STELLMAKER M P, et al. Stimuli-responsive controlled-release delivery system based on mesoporous silica nanorods capped with magnetic nanoparticles[J]. Angew Chem Int Ed, 2005, 44(32): 5038-5044.
[9] WU Q, LIU C, FAN L, et al. Heparinized magnetic mesoporous silica nanoparticles as multifunctional growth factor delivery carriers [J]. Nanotechnology , 2012, 23(48):485-703.
[10] XIA T A, KOVOCHICH M, LIONG M, et al. Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs [J]. ACS Nano, 2009, 3(10): 3273-3786.
[11] SCHMIDT N O, WESTPHAL M, HAGEL C. Levels of vascular endothelial growth factor, hepatocyte growth factor/scatter factor and basic fibroblast growth factor in human gliomas and their relation to angiogenesis [J]. Int J Cancer, 1999, 84(1):10-18.
[12] GERBER H P. Anti-angiogenesis: Biology is the foundation for therapy [J]. Drug Discovery Today, 2003, 8(8):344-346.
[13] SEGHEZZI G, PATEL S, REN C J, et al. Fibroblast growth factor-2 (FGF-2) induces vascular endothelial growth factor (VEGF) expression in the endothelial cells of forming capillaries: An autocrine mechanism contributing to angiogenesis [J]. J Cell Biol, 1998,141(7):1659-1673.
[14] PARK K, LEE G Y, KIM Y S, et al. Heparin-deoxycholic acid chemical conjugate as an anticancer drug carrier and its antitumor activity [J]. J Controlled Release, 2006,114(3):300-306.
[15] CHEN Y, CHEN H R, SHI J L. In vivo bio-safety evaluations and diagnostic/therapeutic applications of chemically designed mesoporous silica nanoparticles[J]. Adv Mater,2013,25:3144-3176.
[16] HE Q J, ZHANG Z W, GAO F, et al. In vivo biodistribution and urinary excretion of mesoporous silica nanoparticles: Effects of particle size and PEGylation[J]. Small, 2011,7(2):271-280.
[17] HUANG X L, LI L L, LIU T L, et al. The shape effect of mesoporous silica nanoparticles on biodistribution, clearance, and biocompatibility in vivo[J]. ACS Nano,2011, 5(7):5390-5399.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
国家自然科学基金资助项目(21073054)
{{custom_fund}}
PDF(1033 KB)
