药学学报, 2021, 56(5): 1470-1477
李小畅, 陈焘熙, 李清晨, 刘杨佳, 叶田田, 王淑君. 经降解酶修饰的分子印迹干凝胶用于多巴胺选择性吸附和降解[J]. 药学学报, 2021, 56(5): 1470-1477.
LI Xiao-chang, CHEN Tao-xi, LI Qing-chen, LIU Yang-jia, YE Tian-tian, WANG Shu-jun. Degrading enzyme modified molecularly imprinted xerogel for selective adsorption and degradation of dopamine[J]. Acta Pharmaceutica Sinica, 2021, 56(5): 1470-1477.

李小畅1, 陈焘熙2, 李清晨1, 刘杨佳2, 叶田田2*, 王淑君2*
1. 沈阳药科大学中药学院, 辽宁 沈阳 110016;
2. 沈阳药科大学药学院, 辽宁 沈阳 110016
近年来,因使用成瘾药物产生过量多巴胺(DA)引起关注并亟需解决。分子印迹干凝胶聚合物(molecularly imprinted xerogel polymers,MIXPs)由仿生溶胶-凝胶法制备而成,即聚乙烯亚胺、模板分子DA自组装并以非共价氢键与四甲氧基硅烷交联,洗脱模板DA会留下印迹位点。然后将单胺氧化酶进行MIXPs固定化,得到经酶固定化后的分子印迹干凝胶(monoamine oxidase immobilized MIXPs,MAO-MIXPs),通过制备的人工脑脊液在体外模拟脑中多巴胺表达环境,考察其对多巴胺的选择吸附性能和降解性能,并以吸附性能和降解性能为指标,对MAO-MIXPs进行处方优化,确定最佳处方为:DA 40 mg、聚乙烯亚胺0.6 mL与单胺氧化酶2.5 mg·g-1。扫描电子显微镜、差示热量扫描仪和傅立叶变换红外光谱对MAO-MIXPs的性状和理化性质进行表征,Brunner-Emmet-Teller多分子层吸附公式(BET)和兰格缪尔吸附公式(Langmuir)模型模拟,其吸附行为倾向于单层吸附。本研究成功制备了可选择性识别、吸附并降解多巴胺的分子印迹干凝胶聚合物。
关键词:    分子印迹聚合物      选择性      吸附      多巴胺      单胺氧化酶      溶胶-凝胶法     
Degrading enzyme modified molecularly imprinted xerogel for selective adsorption and degradation of dopamine
LI Xiao-chang1, CHEN Tao-xi2, LI Qing-chen1, LIU Yang-jia2, YE Tian-tian2*, WANG Shu-jun2*
1. School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China;
2. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
In recent years, the overexpression dopamine (DA) due to the use of addictive drugs has caused concern and urgently needs to be addressed. The method used in our study is known as biomimetic sol-gel synthesis. We undertook the experiment to develop molecularly imprinted xerogel polymers (MIXPs) through template molecules dopamine polymerized with polyethyleneimine (PEI), then self-assembled and crosslinked with tetramethoxysilane (TMOS) in the form of non-covalent hydrogen bonds by using biomimetic sol-gel process, and then eluted template DA will leave a blotting site. Monoamine oxidase immobilized MIXPs (MAO-MIXPs) was obtained by coating monoamine oxidase onto MIXPs. The synthesis optimization of MAO-MIXPs was finally set as the ratio of DA template, PEI and MAO coating (DA 40 mg, PEI 0.6 mL, MAO 2.5 mg�g-1) to achieve highly selective adsorption toward DA in artificial cerebrospinal fluid based on the adsorption performance and degradation performance. The micromorphologies and physical-chemical properties of MAO-MIXPs were characterized by scanning electron microscopy, differential scanning calorimeter and Fourier transform infrared spectroscopy, and then amount of adsorption was calculated with adsorption equation. Simultaneously, the Brunner-Emmet-Teller (BET) and Langmuir model were simulated. It was found that the adsorption behavior tended to be monolayer adsorption. This new molecularly imprinted polymer demonstrated potential dopamine expression regulation for highly selective recognition, adsorption and degradation of dopamine.
Key words:    molecularly imprinted polymer    selective    adsorption    dopamine    monoamine oxidase    sol-gel process   
收稿日期: 2020-12-21
DOI: 10.16438/j.0513-4870.2020-1935
基金项目: 国家重点项目,军委后勤保障部应用基础研究重点项目(BWS16J007);国家自然科学基金资助项目(81703455,81973494).
通讯作者: 叶田田,王淑君,Tel:86-24-43520518,E-mail:1252116911@qq.com;王淑君,E-mail:729587208@qq.com
Email: 1252116911@qq.com;729587208@qq.com
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陈焘熙  在本刊中的所有文章
李清晨  在本刊中的所有文章
刘杨佳  在本刊中的所有文章
叶田田  在本刊中的所有文章
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[1] Wu ZH, Chai ML, Hou JP, et al. Recent advances and perspective in the study of the nano-reinforcing materials for molecular imprinting of proteins[J]. Acta Pharm Sin (药学学报), 2015, 50:15-20.
[2] Wang X, Wang YH, Liu S, et al. Construction of the brain-targeting drug carrier through imprinting of nicotinic acetylcholine receptor α7[J]. Acta Pharm Sin (药学学报), 2017, 52:488-493.
[3] BelBruno JJ. Molecularly imprinted polymers[J]. Chem Rev, 2018, 119:94-119.
[4] Chen LX, Wang XY, Lu WH. Molecular imprinting:perspectives and applications[J]. Chem Soc Rev, 2016, 45:2137-2211.
[5] Zhang HQ. Water-compatible molecularly imprinted polymers:promising synthetic substitutes for biological receptors[J]. Polymer, 2014, 55:699-714.
[6] Hu YL, Pan JL, Zhang KG, et al. Novel applications of molecularly imprinted polymers in sample preparation[J]. Trend Analyt Chem, 2013, 43:37-52.
[7] Peng J, Tang F, Zhou R. New techniques of on-line biological sample processing and their application in the field of biopharmaceutical analysis[J]. Acta Pharm Sin B, 2016, 6:540-551.
[8] Gao BJ, An FQ, Zhu Y. Novel surface ionic imprinting materials prepared via couple grafting of polymer and ionic imprinting on surfaces of silica gel particles[J]. Polymer, 2007, 48:2288-2297.
[9] Kadhirvel P, Azenha M, Silva AF, et al. Chromatographycally efficient microspherical composites of molecularly imprinted xerogels deposited inside mesoporous silica[J]. J Chromatog A, 2014, 1355:158-163.
[10] Lofgreen JE, Ozin GA. Controlling morphology and porosity to improve performance of molecularly imprinted sol-gel silica[J]. Chem Soc Rev, 2014, 43:911-933.
[11] Shaerzadeh F, Streit WJ, Heysieattalab S, et al. Methamphetamine neurotoxicity, microglia, and neuroinflammation[J]. J Neuroinflammation, 2018, 15:341.
[12] Park EJ, Min YG, Kim GW, et al. Pathophysiology of brain injuries in acute carbon monoxide poisoning:a novel hypothesis[J]. Med Hypoth, 2014, 83:186-189.
[13] Begieneman M, Horst ET, Rijvers L, et al. Dopamine induces lipid accumulation, NADPH oxidase-related oxidative stress and a pro-inflammatory status of the plasma membrane in H9C2 cells[J]. Am J Physiol Heart C, 2016, 311:1097-1107.
[14] Xue X, Yang JY, He Y, et al. Aggregated single-walled carbon nanotubes attenuate the behavioural and neurochemical effects of methamphetamine in mice[J]. Nat Nanotechnol, 2016, 11:613-620.
[15] Ribeiro JA, Fernandes P, Pereira CM, et al. Electrochemical sensors and biosensors for determination of catecholamine neurotransmitters:a review[J]. Talanta, 2016, 160:653-679.
[16] Nagai Y, Yudasaka M, Kataura H, et al. Brighter near-IR emission of single-walled carbon nanotubes modified with a cross-linked polymer coating[J]. Chem Commun, 2019, 55:6854-6857.
[17] Meran M, Akkus PD, Kurkcuoglu O, et al. Noncovalent pyrene-polyethylene glycol coatings of carbon nanotubes achieve in vitro biocompatibility[J]. Langmuir, 2018, 34:12071-12082.
[18] Movia D, Canto ED, Giordani S. Purified and oxidized single-walled carbon nanotubes as robust near-IR fluorescent probes for molecular imaging[J]. J Phys Chem C, 2010, 114:18407-18413.
[19] Cicchetti R, Divizia M, Valentini F, et al. Effects of single-wall carbon nanotubes in human cells of the oral cavity:geno-cytotoxic risk[J]. Toxicol In Vitro, 2011, 25:1811-1819.
[20] Pei MY. The influence of ephedrine on the activity of amineoxidase[J]. Acta Pharm Sin (药学学报), 1964, 834-836.
[21] Yang Z, Wang X, Yang J, et al. Aberrant CpG methylation mediates abnormal transcription of MAO-A induced by acute and chronic L-3,4-dihydroxyphenylalanine administration in SH-SY5Y neuronal cells[J]. Neurotox Res, 2017, 31:334-347.
[22] Aguirre-Martinez GV, Andre C, Gagne F, et al. The effects of human drugs in Corbicula fluminea. Assessment of neurotoxicity, inflammation, gametogenic activity, and energy status[J]. Ecotoxicol Environ Safe, 2017, 148:652-663.
[23] Li J, Xu L, Wang HY, et al. Comparison of bare and amino modified mesoporous silica@poly(ethyleneimine)s xerogel as indomethacin carrier:superiority of amino modification[J]. Mat Sci Eng C Mater, 2016, 59:710-716.
[24] Spector R, Snodgrass SR, Johanson CE. A balanced view of the cerebrospinal fluid composition and functions:focus on adult humans[J]. Exp Neurol, 2015, 273:57-68.
[25] Pathak A, Gupta BD. Ultra-selective fiber optic SPR platform for the sensing of dopamine in synthetic cerebrospinal fluid incorporating permselective nafion membrane and surface imprinted MWCNTs-PPy matrix[J]. Biosens Bioelectron, 2019, 133:205-214.
[26] Tian JJ, Yu YT, Zhao LJ, et al. Mesoporous silica solidifying volatile oil from Bupleuri radix and forsythiae fructus and its micromeritic properties[J]. Acta Pharm Sin (药学学报), 2019, 54:1493-1501.
[27] An FQ, Gao BJ, Feng XQ. Adsorption and recognizing ability of molecular imprinted polymer MIP-PEI/SiO2 towards phenol[J]. J Hazard Mater, 2008, 157:286-292.
[28] Langmuir I. The adsorption of gases on plane surfaces of glass, mica and platinum[J]. J Am Chem Soc, 1918, 40:1361-1403.
[29] Anirudhan TS, Christa J, Deepa JR. Extraction of melamine from milk using a magnetic molecularly imprinted polymer[J]. Food Chem, 2017, 227:85-92
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