溶菌酶响应纳米钻石载药体系制备及其与HepG2细胞作用

doi:10.11944/j.issn.1000-0518.2019.10.190112

摘要/Abstract

摘要：

通过缩水甘油(GLY)与阿霉素(DOX)发生开环反应,赋予阿霉素活性羟基基团,以氨基己酸(ACA)为桥梁,通过共价键合方法将缩水甘油化阿霉素(GLY-DOX,GDOX)偶联于氨基己酸化纳米钻石(ND-ACA)载体上,获得具有溶菌酶响应特性的ND-ACA-GLY-DOX(NAGD)药物输送体系。采用荧光光谱法测定了ND表面偶联ACA和DOX的量分别为(185±10.0) μg/mg和(115±5.2) μg/mg。体外释药发现NAGD在生理环境(pH=7.4)中药物释放量很低,而在肿瘤细胞溶酶体环境中(溶菌酶存在下),酯键水解断裂,大量释放DOX。以肝癌细胞HepG2为模型,采用细胞形态测试法表明NAGD可有效杀死肿瘤细胞。上述研究结果表明,NAGD可作为一种良好的药物输送体系,并为共价偶联药物开拓新思维。

关键词: 纳米钻石, 氨基己酸, 缩水甘油, 阿霉素, 溶菌酶响应

Abstract:

Glycidol(GLY) and doxorubicin(DOX) were coupled to ACAylated nanodiamond(ND) carrier to obtain nanodiamond-aminocaproic acid-glycidol-doxorubicin (ND-ACA-GLY-DOX, NAGD) drug delivery system through ester bond. The amounts of ACA and DOX coupled to the surface of the ND were (185±10.0) μg/mg and (115±5.2) μg/mg, respectively, as determined by fluorescence spectroscopy. The results showed that the amount of NAGD released was very low in the physiological environment(pH=7.4), while the ester bond was hydrolytically cleaved and a large amount of DOX was released in the presence of lysozyme in the lysosome environment of the tumor cells. Using liver cancer cells as the model, the cell morphology test showed that NAGD could effectively kill tumor cells. The above results indicate that NAGD can be used as a good drug delivery system.

Key words: nanodiamond, aminocaproic acid, glycidol, doxorubicin, lysozyme responsive

李林, 宋吉祥, 李英奇, 张彩凤. 溶菌酶响应纳米钻石载药体系制备及其与HepG2细胞作用[J]. 应用化学, 2019, 36(10): 1109-1117.

LI Lin, SONG Jixiang, LI Yingqi, ZHANG Caifeng. Preparation of Lysozyme-Responsive Nanodiamond Drug-Loading System and the Effect on HepG2 Cells[J]. Chinese Journal of Applied Chemistry, 2019, 36(10): 1109-1117.

参考文献

[1]	GolobSchwarzl N,Krassnig S,Toeglhofer A M,et al. New Liver Cancer Biomarkers: PI3K/AKT/mTOR Pathway Members and Eukaryotic Translation Initiation Factors[J]. Eur J Cancer,2017,83:56-70.
[2]	Zhang H L,Song Y,Yang H M,et al. Tumor Cell-intrinsic Tim-3 Promotes Lver Cancer via NF-κB/IL-6/STAT3 Axis[J]. Oncogene,2018,37:2456-2468.
[3]	Maucort-Boulch D,de Martel C,Franceschi S,et al. Fraction and Incidence of Liver Cancer Attributable to Hepatitis B and C Viruses Worldwide[J]. Int J Cancer,142:2471-2477.
[4]	Yin H S,Que R S,Liu C Y,et al. Survivin-Targeted Drug Screening Platform Identifies a Matrine Derivative WM-127 as a Potential Therapeutics Against Hepato Cellular Carcinoma[J]. Cancer Lett,2018,425:54-64.
[5]	Fraser S,Antonella V,Qiu Y Q,et al. A Prototype Therapeutic Capsule Endoscope for Ultrasound-Mediated Targeted Drug Delivery[J]. J Med Robot Res,2018,3:1-13.
[6]	Wang Y R,Yang S Y,Chen G X,et al. Barbaloin Loaded Polydopamine-Polylactide-TPGS(PLA-TPGS) Nanoparticles Against Gastric Cancer as a Targeted Drug Delivery System:Studies in Vitro and in Vivo[J]. Biochem Biophys Res Commun,2018,499(1):8-16.
[7]	Umberto C,Hsia F C,Danielle V,et al. Mesoscopic Physical Removal of Material Using Sliding Nanodiamond Contacts[J]. Sci Rep,2018,8:2994-3005.
[8]	Larsson K,Tian Y.Effect of Surface Termination on the Reactivity of Nano-sized Diamond Particle Surfaces for Bio Applications[J]. Carbon,2018,134:244-254.
[9]	Xi G F,Robinson E,Mania-Farnell B,et al. Convection-Enhanced Delivery of Nanodiamond Drug Delivery Platforms for Intracranial Tumor Treatment[J]. Nanomed-Nanotechnol Biol Med,2014,10:381-391.
[10]	Chow E K,Zhang X Q,Chen M,et al. Nanodiamond Therapeutic Delivery Agents Mediate Enhanced Chemoresistant Tumor Treatment[J]. Sci Transl Med,2011,3:73 ra 21.
[11]	Wang D X,Tong Y L,Li Y Q,et al. PEGylated Nanodiamond for Chemotherapeutic Drug Delivery[J]. Diamond Relat Mater,2013,36:26-34.
[12]	Dong Y,Cao R X,Li Y Q,et al. Folate-Conjugated Nanodiamond for Tumor-Targeted Drug Delivery[J]. RSC Adv,2015,5:82711-82716.
[13]	CAO Ruixia,TIAN Zhimei,WANG Dongxin,et al. Preparation of Folic Acid Functionalized Nanodiamonds Loading Drug and Its Targeted Research of C6 Cells[J]. J Shanxi Univ,2014,37(1):91-97(in Chinese). 曹瑞霞,田志梅,王东新,等. 叶酸功能化ND载药体系的制备及其对C6细胞靶向性研究[J]. 山西大学学报,2014,37(1):91-97.

[1]	黄旭娟, 王婷, 丁正青, 杨欣欣, 蔡照胜, 商士斌. 脱氢枞氧基聚氧乙烯缩水甘油醚接枝羟乙基壳聚糖水凝胶制备及其性能[J]. 应用化学, 2022, 39(9): 1421-1428.
[2]	齐延新, 黄宇彬, 金宁一. 黄体酮纳米胶束构建及体外释放行为[J]. 应用化学, 2020, 37(11): 1340-1342.
[3]	弓韬, 黄昱, 郭国英, 苏丹, 梁文婷, 董川. 线性麦芽糊精聚合物功能化Fe₃O₄纳米复合物药物载体的合成和应用[J]. 应用化学, 2019, 36(2): 161-169.
[4]	于畅,邵帅,李贺杰,刘国锋,丁彬彬,马平安,林君. 上转换纳米粒子结合DNA链式扩增技术在阿霉素光控释放中的应用[J]. 应用化学, 2018, 35(12): 1485-1491.
[5]	于畅, 邵帅, 李贺杰, 刘国锋, 丁彬彬, 马平安, 林君. 上转换纳米粒子结合DNA链式扩增技术在阿霉素光控释放中的应用[J]. 应用化学, 2018, 35(12): 0-0.
[6]	张奕, 巫凌波, 胡倩, 陈宝欣, 吴柏杨, 薛巍. 功能化修饰的超支化聚缩水甘油醚在药物载体领域的应用[J]. 应用化学, 2015, 32(4): 367-378.
[7]	曹林交, 高保娇, 胡伟民. 生物碱分子表面印迹聚合物材料的设计与制备及其分子识别特性[J]. 应用化学, 2014, 31(12): 1390-1398.
[8]	郭文彦, 赵明刚, 郝爱友. 低取代度两亲性β-环糊精及其水相中纳米球的制备[J]. 应用化学, 2013, 30(03): 260-264.
[9]	张毅, 韩晓燕, 赵培莉, 郭炜毅, 张政朴. 磺化改性聚四氟乙烯纤维固相萃取-高效液相色谱联用测定奶制品中的三聚氰胺[J]. 应用化学, 2011, 28(04): 448-453.
[10]	张跃华, 王南平, 张其平, 王清明, 陆天虹. β-环糊精与阿霉素相互作用荧光光谱[J]. 应用化学, 2011, 28(03): 343-348.
[11]	郭兴家, 郭闯, 姜玉春, 佟健, 康平利, 安如彬, 韩晓伟. 光谱法研究氨基己酸与牛血清白蛋白的相互作用[J]. 应用化学, 2010, 27(10): 1192-1198.
[12]	李玉慧,彭婷婷,张丽,欧阳丽,谢青季,苏孝礼,马铭. 羧甲基壳聚糖磁性纳米粒子的合成及应用[J]. 应用化学, 2010, 27(01): 87-91.
[13]	刘秀英, 张超灿, 崔卫钢, 徐卫林. 一种改进的烯丙基缩水甘油醚的合成方法[J]. 应用化学, 2009, 26(3): 370-372.
[14]	江艳华. 稀土三元催化剂作用下正辛酸缩水甘油酯-二氧化碳-环氧丙烷的三元共聚合研究[J]. 应用化学, 2009, 26(07): 770-774.
[15]	慕春明, 史铁钧, 史先磊. H2O2环氧化TAIC制备TGIC[J]. 应用化学, 2008, 25(9): 1090-1094.