功能化修饰磁性分子印迹纳米平台的构建及其局部去势治疗性能研究

引用本文: 宋慧佳, 张海频, 张佩, 王超峰, 豆晓杰, 陈小艺, 高瑞霞. 功能化修饰磁性分子印迹纳米平台的构建及其局部去势治疗性能研究[J]. 分析化学, 2022, 50(4): 602-612. doi: 10.19756/j.issn.0253-3820.210832 shu

Citation: SONG Hui-jia, ZHANG Hai-pin, ZHANG Pei, WANG Chao-feng, DOU Xiao-jie, CHEN Xiao-yi, GAO Rui-xia. Construction of Functionalized Magnetic Molecularly Imprinted Nano-platform and Its Performance in Local Castration Therapy[J]. Chinese Journal of Analytical Chemistry, 2022, 50(4): 602-612. doi: 10.19756/j.issn.0253-3820.210832 shu

功能化修饰磁性分子印迹纳米平台的构建及其局部去势治疗性能研究

宋慧佳 ^1, ,
张海频 ^2, ,
张佩 ^2, ,
王超峰 ^1, ,
豆晓杰 ^2, ,
陈小艺 ^2, ,
高瑞霞 ^{1,
,}

1.
西安交通大学化学学院, 西安 710049;2 西安交通大学医学部, 西安 710061

通讯作者: 高瑞霞,E-mail:ruixiagao@xjtu.edu.cn

基金项目:
陕西省自然科学基金项目(Nos.2020JM-066,2020JQ-019)资助

摘要: 无机纳米复合材料的构建及其在肿瘤治疗/诊断领域的应用是新型纳米诊疗药物的研究热点。前列腺癌去势治疗药物主要是通过抑制全身雄激素的产生或阻滞雄激素与雄激素受体(AR)结合发挥作用,但具有全身性副作用。因此,开发新型去势策略以选择性去除局部组织的睾酮(Testosterone,TSTO),对于增强治疗效果并降低全身副作用具有重要意义。分子印迹聚合物因其具有高选择性也被为“人工抗体”。本研究以功能化修饰磁性纳米粒子为核,采用两步固定模板法和表面印迹策略,利用疏水相互作用、π–π堆积和氢键等作用力构建对TSTO具有高亲和力、高选择性识别和摄取能力的磁性纳米平台(T/AO-MMIPs)。功能化修饰后的载体克服了载体表面功能基团匮乏的缺陷,增强了载体与模板分子的亲和力。T/AO-MMIPs通过高通透性和滞留(EPR)效应被动靶向前列腺癌,利用表面印迹孔穴选择性捕获细胞内部TSTO,阻断其与AR的结合,显著抑制AR核易位,实现对前列腺癌细胞的局部去势治疗。上皮永生化细胞SV-HUC-1经处理后未出现明显的细胞增殖抑制现象。因此,构建的T/AO-MMIPs纳米平台具有高选择性和良好的生物安全性,为前列腺癌局部去势治疗提供了新的研究策略。

关键词:

English

Construction of Functionalized Magnetic Molecularly Imprinted Nano-platform and Its Performance in Local Castration Therapy

1.
School of Chemistry, Xi’an Jiaotong University, Xi’an 710049, China;2 School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China

Corresponding author: GAO Rui-xia, ruixiagao@xjtu.edu.cn

Received Date: 10 November 2021
Revised Date: 06 March 2022
Fund Project:
Supported by the Natural Science Foundation of Shaanxi Province,China(Nos. 2020JM-066, 2020JQ-019)

Abstract: The current clinical castration treatment drugs for prostate cancer are mainly focus on the reduction of systemic androgen or blocking their binding to androgen receptor(AR). However, due to the complexity of signal pathway activation, developing new castration methods to achieve selective removal of androgen from local tissues of prostate cancer is of great significance to enhance the therapeutic effect and reduce systemic side effects. In this work, 3-aminopropyltriethoxysilane(APTES) and octylmethoxysilane(OTMS) were used to modify magnetic nanoparticles to prepare amphiphilic nanoparticles(AO-MNPs). The prepared AO-MNPs enhanced the affinity of carriers towards template testosterone(TSTO), benefiting from the function of the amino and hydrophobic alkyl chain. And then, AO-MNPs was used as the core, TSTO as the template molecule, and dopamine(DA) as the functional monomer to prepared superparamagnetic core-shell testosterone magnetic molecularly imprinted polymers(T/AO-MMIPs) by a two-step template immobilization method. The strategy of two-step immobilization template method not only synergistically enhanced the affinity of the imprinted holes for TSTO, but also made the imprinted holes well arranged in an orderly and regular distribution on the surface of the carrier. Thus, the fabricated T/AO-MMIPs were evaluated to possess high adsorption amount and good selectivity, which played an important role in the selective removal of specific biomolecules from complex biological tissues. When T/AO-MMIPs were taken up by prostate cancer tissue through EPR, they could selectively adsorb the inter TSTO molecules in cells, thereby blocking the combination of TSTO and AR, inhibiting AR activity and exerting prostate cancer tumor growth inhibitory effect, while no obvious effect on normal cells. The as-prepared T/AO-MMIPs nanoplatform provided a new research strategy for enhancing the treatment of prostate cancer castration.

Key words:

Surface molecular imprinting
/ Functional modification
/ Specific recognition
/ Androgen receptor nuclear translocation
/ Castration therapy

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1.
沈阳化工大学材料科学与工程学院沈阳 110142

功能化修饰磁性分子印迹纳米平台的构建及其局部去势治疗性能研究

通讯作者: 高瑞霞,E-mail:ruixiagao@xjtu.edu.cn

English

Construction of Functionalized Magnetic Molecularly Imprinted Nano-platform and Its Performance in Local Castration Therapy

Corresponding author: GAO Rui-xia, ruixiagao@xjtu.edu.cn

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

功能化修饰磁性分子印迹纳米平台的构建及其局部去势治疗性能研究

通讯作者: 高瑞霞,E-mail:ruixiagao@xjtu.edu.cn

English

Construction of Functionalized Magnetic Molecularly Imprinted Nano-platform and Its Performance in Local Castration Therapy

Corresponding author: GAO Rui-xia, ruixiagao@xjtu.edu.cn

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

CCS Chemistry：颜徐州、鲍哲南：你的皮肤可能是一片SPMs