基于含苯硼酸聚合物的双响应性胶束

doi:10.7503/cjcu20140270

高等学校化学学报 ›› 2014, Vol. 35 ›› Issue (7): 1570.doi: 10.7503/cjcu20140270

基于含苯硼酸聚合物的双响应性胶束

孙小成, 杨浩, 王建祖, 马如江(), 安英丽, 史林启

南开大学高分子化学研究所, 功能高分子材料教育部重点实验室, 天津化学化工协同创新中心, 天津 300071

收稿日期:2014-03-25 出版日期:2014-07-10 发布日期:2014-05-19
作者简介:联系人简介: 马如江, 男, 博士, 副研究员, 主要从事功能高分子研究. E-mail: marujiang@nankai.edu.cn
基金资助:
国家自然科学基金(批准号: 21274001, 91127045, 51390483)、国家“九七三”计划项目(批准号: 2011CB932503)和教育部长江学者和创新团队发展计划项目(批准号: IRT1257)资助

Dual-responsive Micelles Based on Boronicacid-modified Polymer^†

SUN Xiaocheng, YANG Hao, WANG Jianzu, MA Rujiang^*(), AN Yingli, SHI Linqi

Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Collaborative Innovation Center of Chemical Science and Engineering(Tianjin), Nankai University, Tianjin 300071, China

Received:2014-03-25 Online:2014-07-10 Published:2014-05-19
Contact: MA Rujiang E-mail:marujiang@nankai.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China(Nos.21274001, 91127045, 51390483), the National Basic Research Program of China(No.2011CB932503), the Program for Changjiang Scholars of China and Innovative Research Team in University of China(NoIRT1257)

摘要/Abstract

摘要：

分别合成了苯硼酸修饰的嵌段聚合物聚乙二醇-b-聚(天冬氨酸-co-天冬酰氨基苯硼酸)[PEG-b-P(Asp-co-AspPBA)]和含有二硫键及多元二醇的小分子3,3'-二硫代二[1,2(S)-丙二醇](DTBPD). 以DTBPD为小分子交联剂, 通过二醇单元与苯硼酸之间的共价酯化作用, 诱导PEG-b-P(Asp-co-AspPBA)自组装形成以苯硼酸环酯为核、 PEG为壳的交联胶束. 利用核磁共振氢谱和激光光散射对胶束的结构进行了表征, 并分别测定了该胶束在葡萄糖和氧化-还原试剂二硫苏糖醇(DTT)刺激下的响应行为. 结果表明, DTBPD可与聚合物链上的苯硼酸形成苯硼酸环酯, 通过交联作用诱导聚合物形成胶束. 交联度不同时, 胶束对于外界刺激(葡萄糖和DTT的响应行为也不同: 随着DTT和葡萄糖浓度的增加, 交联度高的胶束只发生响应性溶胀, 交联度低的胶束则先溶胀, 之后溶胀程度较大的部分胶束则发生解体, 导致胶束的平均粒径减小.

关键词: 苯硼酸, 二硫键, 交联胶束, 葡萄糖响应, 氧化还原响应, 双响应性胶束

Abstract:

Phenylboronic acid modified polymer poly(ethylene glycol)-b-poly(aspartic acid-co-aspartamidophenylboronic acid)[PEG-b-P(Asp-co-AspPBA)] as well as a cross-linker 3,3'-dithiobis[1,2(S)-propanediol](DTBPD) which contained disulfide bond and dual-diol groups was successfully synthesized. PEG-b-P(Asp-co-AspPBA) could be mildly cross-linked by DTBPD based on the reaction of PBA and the dual-diol groups, leading to the formation of a novel dual-responsive micelle with boronic ester core and PEG shell. The structure, morphology, and the glucose/redox dual-responsive behavior of the micelles were systematically investigated by nuclear magnetic resonance(NMR) spectrum and dynamic laser light scattering(DLS). It was demonstrated that the ratio of diol to PBA(D∶B) had influence on the dual-responsive behavior of the micelles. At higher ratio of D∶B, only responsive swelling of micelles was observed. While for the micelles with lower ratio of D∶B, larger degree of swelling happened and the micelles gradually dissociated under higher concentrations of glucose ordithiothreitol(DTT). This kind of dual-responsive micelles may find application in drug delivery in the future.

Key words: Boronic acid, Disulfidebond, Cross-linked micelle, Glucose-response, Redox-response, Dual-responsive micelle

中图分类号:

O631

TrendMD:

孙小成, 杨浩, 王建祖, 马如江, 安英丽, 史林启. 基于含苯硼酸聚合物的双响应性胶束. 高等学校化学学报, 2014, 35(7): 1570.

SUN Xiaocheng, YANG Hao, WANG Jianzu, MA Rujiang, AN Yingli, SHI Linqi. Dual-responsive Micelles Based on Boronicacid-modified Polymer^†. Chem. J. Chinese Universities, 2014, 35(7): 1570.

图/表 9

Scheme 1 Schematic illustration of DTBPD cross-linked micelles to response to glucose and DTT

Scheme 2 Synthesis routes of PEG-b-P(Asp-co-AspAPBA)

Scheme 3 Synthesis route of DTBPD

Fig.1 1H NMR spectra of PEG114-b-PBLA64 in CDCl3(a), PEG114-b-PAsp64 in D2O(b), PEG114-b-P(Asp37-co-AspAPBA27) in NaDO/D2O(c)

Fig.2 1H NMR spectra of α-thioglycerol(a) and DTBPD(b) in CD3OD

Fig.3 1H NMR spectra of DTBPD(a), PEG-b-P(Asp-co-AspAPBA)(b),PEG-b-P(Asp-co-AspAPB) micelles cross-linked by DTBPD in CD3OD(c)

Fig.4 Hydrodynamic size distributions as a function of the ratio of boronic acid [—B(OH)2] to diol(B∶D) with DTBPD as a cross-linker at a concentration of 0.2 mg/mL PEG-b-P(Asp-co-AspAPBA) in methanol solution(A) and TEM image of PEG-b-P(Asp-co-AspAPBA) micelles cross-linked by DTBPD at the B∶D ratio of 1∶1.5(B)

Fig.5 Hydrodynamic size distributions(A, C) and normalized light scattering intensity(B, D) of PEG-b-P(Asp-co-AspAPBA) micelles cross-linked by DTBPD at the B∶D ratios of 1∶3(A, B) and 1∶2(C, D) under various glucose concentrations in methanol solutions Concentration of glucose/(mg·mL-1): a. 0; b. 2; c. 5; d. 10.

Fig.6 Hydrodynamic size distributions(A, C) and normalized light scattering intensities(B, D) of PEG-b-P(Asp-co-AspAPBA) micelles cross-linked by DTBPD at the B∶D ratios of 1∶3(A, B) and 1∶2(C, D) under various DTT concentrations in methanol solutions Concentration of DTT/(mmol·L-1): a. 0; b. 2; c. 5; d. 10.

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基于含苯硼酸聚合物的双响应性胶束

Dual-responsive Micelles Based on Boronicacid-modified Polymer^†

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基于含苯硼酸聚合物的双响应性胶束

Dual-responsive Micelles Based on Boronicacid-modified Polymer†

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Dual-responsive Micelles Based on Boronicacid-modified Polymer^†