pH/温度响应型聚合物PMAA-b-PDMAEMA的合成、性能调控及应用

doi:10.16085/j.issn.1000-6613.2023-0267

化工进展 ›› 2024, Vol. 43 ›› Issue (1): 480-489.DOI: 10.16085/j.issn.1000-6613.2023-0267

• 精细化工 • 上一篇

pH/温度响应型聚合物PMAA-b-PDMAEMA的合成、性能调控及应用

孙月¹(), 王斯佳¹(), 吴明侠¹(), 宋先雨²(), 徐首红³

^1.河南中医药大学药学院，河南郑州 450000
^2.重庆三峡学院环境与化学工程学院，重庆 404020
^3.华东理工大学化学与分子工程学院，上海 200237

收稿日期:2023-02-27 修回日期:2023-04-14 出版日期:2024-01-20 发布日期:2024-02-05
通讯作者: 王斯佳,吴明侠,宋先雨
作者简介:孙月（1996—），女，硕士研究生，研究方向为高分子材料。E-mail：sy19503872383@163.com。
基金资助:
国家自然科学基金(22208089);河南省自然科学基金(222300420217)

Synthesis, performance regulation and application of pH/temperature responsive polymer PMAA-b-PDMAEMA

SUN Yue¹(), WANG Sijia¹(), WU Mingxia¹(), SONG Xianyu²(), XU Shouhong³

^1.College of Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou 450000, Henan, China
^2.College of Environment and Chemical Engineering, Chongqing Three Gorges University, Chongqing 404020, China
^3.School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China

Received:2023-02-27 Revised:2023-04-14 Online:2024-01-20 Published:2024-02-05
Contact: WANG Sijia, WU Mingxia, SONG Xianyu

摘要/Abstract

摘要：

以甲基丙烯酸叔丁酯（tBMA）、甲基丙烯酸N,N-二甲氨基乙酯（DMAEMA）为原料，通过原子转移自由基聚合（ATRP）法合成了两亲性嵌段聚合物聚甲基丙烯酸叔丁酯-b-聚甲基丙烯酸N,N-二甲氨基乙酯（PtBMA-b-PDMAEMA），将其进行水解得到功能可调控的pH/温度双重响应性共聚物PMAA-b-PDMAEMA。采用核磁共振波谱（¹H NMR）、傅里叶变换红外光谱（FTIR）、紫外可见分光光度计（UV-Vis）、动态光散射（DLS）及荧光分光光度计等对共聚物的结构及性能进行表征和分析，研究共聚物的嵌段比、分子量及溶液pH对响应性能的调控，并初步考察了共聚物的抗肿瘤潜能。研究结果表明，随着PMAA链段长度增加，等电点向酸性偏移，在等电点时溶液透过率降到最低，表现出良好的pH响应性；温度响应性受溶液pH、分子量及嵌段比的影响，pH越接近等电点、分子量越大，低临界溶液温度（LCST）越低；共聚物与模拟肿瘤细胞膜相互作用后，在pH＝5.5酸性微环境下膜中内容物的泄漏率接近100%，实现了对模拟肿瘤细胞的靶向破坏作用，展现了该共聚物良好的环境响应性。

关键词: 原子转移自由基聚合, 聚合物, 相变, pH/温度响应性, 可调控性

Abstract:

The amphiphilic block polymer poly(tert-butyl methacrylate)-b-poly(2-(dimethylamino)ethyl methacrylate) (PtBMA-b-PDMAEMA) was synthesized by atom transfer radical polymerization (ATRP) using tert butyl methacrylate (tBMA) and N, N-dimethylaminoethyl methacrylate (DMAEMA) as raw materials. The functional controllable pH/temperature dual responsive copolymer PMAA-b-PDMAEMA was obtained by hydrolysis. The structure and properties of the copolymer were characterized and analyzed by nuclear magnetic resonance spectroscopy (¹H NMR), fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectrophotometer (UV-Vis), dynamic light scattering (DLS) and fluorescence spectrophotometer. The regulation of the block ratio, molecular weight and solution pH of copolymers on their response performance was studied, and their anti-tumor potential was preliminarily investigated. The results showed that with the increase of the length of PMAA chain segment, the isoelectric point shifted to acid, and the solution transmittance decreased to the lowest at the isoelectric point, showing good pH responsiveness. Temperature responsiveness was influenced by solution pH, molecular weight and block ratio. As the pH value was approached the isoelectric point and the molecular weight increased, a lower critical solution temperature (LCST) was obtained. After the copolymer interacted with simulated tumor cell membrane, the leakage rate of the contents in the membrane was nearly 100% under pH 5.5 acidic microenvironment, achieving the targeted destruction effect on simulated tumor cells, exhibiting the good environmental responsiveness of the copolymer.

Key words: atom transfer radical polymerization, polymers, phase change, pH/temperature response, adjustability

中图分类号:

孙月, 王斯佳, 吴明侠, 宋先雨, 徐首红. pH/温度响应型聚合物PMAA-b-PDMAEMA的合成、性能调控及应用[J]. 化工进展, 2024, 43(1): 480-489.

SUN Yue, WANG Sijia, WU Mingxia, SONG Xianyu, XU Shouhong. Synthesis, performance regulation and application of pH/temperature responsive polymer PMAA-b-PDMAEMA[J]. Chemical Industry and Engineering Progress, 2024, 43(1): 480-489.

图/表 13

图1 共聚物PMAA-b-PDMAEMA的pH/温度响应性示意图

图2 PMAA-b-PDMAEMA的合成路线

图3 PtBMA、PtBMA-b-PDMAEMA和PMAA-b-PDMAEMA的1H NMR图

表1 不同方法测定的PMAA-b-PDMAEMA的等电点

样品	PMAA _n ∶ PDMAEMA _m	PMAA /%	PDMAEMA /%	pI （浊度法）	pI （zeta电位法）
1	50∶43	0.54	0.46	9.0	9.3
2	50∶2	0.96	0.04	3.2~5.0	3.8
3	30∶22	0.58	0.42	8.8	9.0
4	30∶6	0.83	0.17	6.1	6.0

图4 PtBMA、PtBMA-b-PDMAEMA和PMAA-b-PDMAEMA的红外谱图

图5 均聚物PMAA和共聚物PMAA-b-PDMAEMA水溶液在不同pH条件下的zeta电位变化

图6 不同嵌段比的PMAA-b-PDMAEMA水溶液在不同pH下的透过率曲线

图7 不同pH条件下PDMAEMA30的透过率随温度的变化曲线及溶液pH与LCST的关系

图8 不同pH条件下，共聚物PMAA-b-PDMAEMA的透过率随温度的变化

表2 不同pH条件下共聚物的LCST值 (℃)

pH	PMAA₅₀-b-PDMAEMA₄₃	PMAA₃₀-b-PDMAEMA₂₂
8.5	32	39
9.5	27	37
10.0	37.5	45

图9 pH=9.0时不同聚合度的PDMAEMA的透射率随温度的变化

图10 pH=10.0条件下不同嵌段比的PMAA-b-PDMAEMA透射率随温度的变化

图11 pH=7.4及pH=5.5条件下PMAA-b-PDMAEMA诱导的脂质体中罗丹明6G的泄漏率(a)及作用机理(b)

参考文献 31

1	PANG Xin, JIANG Yue, XIAO Qicai, et al. pH-responsive polymer-drug conjugates: Design and progress[J]. Journal of Controlled Release, 2016, 222: 116-129.
2	KIEVIET B D, SCHÖN P M, VANCSO G J. Stimulus-responsive polymers and other functional polymer surfaces as components in glass microfluidic channels[J]. Lab on a Chip, 2014, 14(21): 4159-4170.
3	王义洲, 刘晔宏, 徐首红, 等. 用于药物载体的多重响应型聚合物分子的设计与合成[J]. 物理化学学报, 2019, 35(8): 876-884.
	WANG Yizhou, LIU Yehong, XU Shouhong, et al. Design and synthesis of multi-responsive copolymers for drug carrier[J]. Acta Physico-Chimica Sinica, 2019, 35(8): 876-884.
4	WEI Ting, YU Qian, CHEN Hong. Responsive and synergistic antibacterial coatings: Fighting against bacteria in a smart and effective way[J]. Advanced Healthcare Materials, 2019, 8(3): e1801381.
5	PATRA Santanu, ROY Ekta, KARFA Paramita, et al. Dual-responsive polymer coated superparamagnetic nanoparticle for targeted drug delivery and hyperthermia treatment[J]. ACS Applied Materials & Interfaces, 2015, 7(17): 9235-9246.
6	XIAO Zecong, SU Zhenwei, HAN Shisong, et al. Dual pH-sensitive nanodrug blocks PD-1 immune checkpoint and uses T cells to deliver NF-κB inhibitor for antitumor immunotherapy[J]. Science Advances, 2020, 6(6): eaay7785.
7	HOREV B, KLEIN M I, HWANG G, et al. pH-activated nanoparticles for controlled topical delivery of farnesol to disrupt oral biofilm virulence[J]. ACS Nano, 2015, 9(3): 2390-2404.
8	DEIRRAM N, ZHANG C, KERMANIYAN S S, et al. pH‐responsive polymer nanoparticles for drug delivery[J]. Macromolecular Rapid Communications, 2019, 40(10): e1800917.
9	KUMAR Parveen, BEHL Gautam, KAUR Sumeet, et al. Tumor microenvironment responsive nanogels as a smart triggered release platform for enhanced intracellular delivery of doxorubicin[J]. Journal of Biomaterials Science Polymer Edition, 2021, 32(3): 385-404.
10	GAO Yuxue, ZONG Shiyu, HUANG Yirong, et al. Preparation and properties of a highly elastic galactomannan-poly(acrylamide- N, N-bis (acryloyl) cysteamine) hydrogel with reductive stimuli-responsive degradable properties[J]. Carbohydrate Polymers, 2020, 231: 115690.
11	ZUO Yanming, YAN Xu, XUE Jingzhe, et al. Enzyme-responsive Ag nanoparticle assemblies in targeting antibacterial against methicillin-resistant staphylococcus aureus[J]. ACS Applied Materials & Interfaces, 2020, 12(4): 4333-4342.
12	BAIER Grit, CAVALLARO Alex, VASILEV Krasimir, et al. Enzyme responsive hyaluronic acid nanocapsules containing polyhexanide and their exposure to bacteria to prevent infection[J]. Biomacromolecules, 2013, 14(4): 1103-1112.
13	YU Yingjie, XU Quan, HE Shasha, et al. Recent advances in delivery of photosensitive metal-based drugs[J]. Coordination Chemistry Reviews, 2019, 387: 154-179.
14	LIU Baitong, PAN Xiaohong, NIE Danyue, et al. Ionic hydrogen-bonded organic frameworks for ion-responsive antimicrobial membranes[J]. Advanced Materials, 2020, 32(48): e2005912.
15	PAVLUKHINA Svetlana, LU Yiming, PATIMETHA Altida, et al. Polymer multilayers with pH-triggered release of antibacterial agents[J]. Biomacromolecules, 2010, 11(12): 3448-3456.
16	CAO Ziquan, WU Hao, DONG Jie, et al. Quadruple-stimuli-sensitive polymeric nanocarriers for controlled release under combined stimulation[J]. Macromolecules, 2014, 47(24): 8777-8783.
17	LIU Y, BUSSCHER H J, ZHAO B, et al. Surface-adaptive, antimicrobially loaded, micellar nanocarriers with enhanced penetration and killing efficiency in staphylococcal biofilms[J]. ACS Nano, 2016, 10(4): 4779-4789.
18	LIU Peng, LI Xuelian, ZHANG Hongxia, et al. pH-responsive spiropyran-based copolymers and their application in monitoring and antibacterial coatings[J]. Progress in Organic Coatings, 2021, 156: 106259.
19	WANG Hongwei, WANG Lei, ZHANG Pengchao, et al. High antibacterial efficiency of pDMAEMA modified silicon nanowire arrays[J]. Colloids and Surfaces B: Biointerfaces, 2011, 83(2): 355-359.
20	CHEN Fang, CHEN Zhuguo, SUN Huizhao, et al. Anion effect on the tunable stability of a thermoresponsive pickering emulsion based on SiO₂-PNIPAM[J]. Acta Physico-Chimica Sinica, 2016, 32(3): 763-770.
21	姚加, 汪青, 童达君, 等. 不同嵌段比的PEG-b-PDMAEMA共聚物在水溶液中的自聚集行为[J]. 物理化学学报, 2007, (10): 1612-1616.
	YAO Jia, WANG Qing, TONG Dajun, et al. Self-aggregation behavior of PEG-b-PDMAEMA copolymers with different block ratios in aqueous solution[J]. Acta Physico-Chimica Sinica, 2007, (10): 1612-1616.
22	DE SOUZA J C, NAVES A F, FLORENZANO F H. Specific thermoresponsiveness of PMMA-block-PDMAEMA to selected ions and other factors in aqueous solution[J]. Colloid and Polymer Science, 2012, 290(13): 1285-1291.
23	HAN Xia, ZHANG Xuxia, ZHU Hongfan, et al. Effect of composition of PDMAEMA-b-PAA block copolymers on their pH- and temperature-responsive behaviors[J]. Langmuir, 2013, 29(4): 1024-1034.
24	WANG Sijia, SUN Yue, XU Shouhong, et al. Novel peptide-polymer conjugate with pH-responsive targeting/disrupting effects on biomembranes[J]. Langmuir, 2021, 37(29): 8840-8846.
25	周西来, 董少波, 兰天宇, 等. 环境响应型共聚物自组装的研究进展[J]. 广东化工, 2021, 48(10): 95-98, 91.
	ZHOU Xilai, DONG Shaobo, LAN Tianyu, et al. Research progress on self-assembly of environmentally responsive copolymers[J]. Guangdong Chemical Industry, 2021, 48(10): 95-98, 91.
26	杨倩丽, 康晓明, 孙静, 等. 刺激响应性聚合物的设计、合成及其应用研究新进展[J]. 化工进展, 2015, 34(8): 3075-3084, 3098.
	YANG Qianli, KANG Xiaoming, SUN Jing, et al. New progress in the design, synthesis and application of stimuli responsive polymers[J]. Chemical Industry and Engineering Progress, 2015, 34(8): 3075-3084, 3098.
27	CHEN Cuixia, CHEN Yucan, YANG Cheng, et al. High selective performance of designed antibacterial and anticancer peptide amphiphiles[J]. ACS Applied Materials & Interfaces, 2015, 7(31): 17346-17355.
28	WANG Sijia, WANG Tong, ZHANG Junqi, et al. Disruption of tumor cells using a pH-activated and thermosensitive antitumor lipopeptide containing a leucine zipper structure[J]. Langmuir, 2018, 34(30): 8818-8827.
29	AROURI Ahmad, DATHE Margitta, BLUME Alfred. Peptide induced demixing in PG/PE lipid mixtures: A mechanism for the specificity of antimicrobial peptides towards bacterial membranes?[J]. Biochimica et Biophysica Acta - Biomembranes, 2009, 1788(3): 650-659.
30	LUO Yanling, YU Wei, XU Feng. pH-responsive PMAA-b-PEG-b-PMAA triblock copolymer micelles for prednisone drug release and release kinetics[J]. Polymer Bulletin, 2012, 69(5): 597-620.
31	BONDAZ Louis, COUSIN Fabrice, MULLER François, et al. pH-sensitive behavior of the PS-b-PDMAEMA copolymer at the air - water interface[J]. Polymer, 2021, 221: 123619.

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pH/温度响应型聚合物PMAA-b-PDMAEMA的合成、性能调控及应用

Synthesis, performance regulation and application of pH/temperature responsive polymer PMAA-b-PDMAEMA

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