化学学报 ›› 2019, Vol. 77 ›› Issue (10): 1036-1044.DOI: 10.6023/A19060226 上一篇    下一篇

研究论文

基于AIE效应的多重刺激响应性聚合物纳米微球的制备及其细胞示踪应用

关晓琳a*(), 王林a, 李志飞a, 刘美娜a, 王凯龙a, 林斌a, 杨学琴a, 来守军b, 雷自强a   

  1. a 西北师范大学 生态环境相关高分子材料教育部重点实验室 甘肃省高分子材料重点实验室 化学化工学院 兰州 730070
    b 兰州文理学院化工学院 兰州 730000
  • 收稿日期:2019-06-21 出版日期:2019-10-15 发布日期:2019-08-13
  • 通讯作者: 关晓琳 E-mail:guanxiaolin@nwnu.edu.cn
  • 基金资助:
    项目受国家自然科学基金(21761032);项目受国家自然科学基金(51363019);生态环境相关高分子材料教育部重点实验室开放基金(KF-18-05)

Preparation of Multi-stimulus Responsive Polymer Nanospheres Based on AIE Effect and Its Cell Tracing Application

Guan, Xiaolina*(), Wang, Lina, Li, Zhifeia, Liu, Meinaa, Wang, Kailonga, Lin, Bina, Yang, Xueqinga, Lai, Shoujunb, Lei, Ziqianga   

  1. a Key Laboratory of Eco-Environment-Related Polymer Materials Ministry of Education, Key Laboratory of Polymer Materials Ministry of Gansu Province, College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou 730070, China
    b School of Chemical Engineering, Lanzhou University of Arts and Science, Lanzhou 730000, China
  • Received:2019-06-21 Online:2019-10-15 Published:2019-08-13
  • Contact: Guan, Xiaolin E-mail:guanxiaolin@nwnu.edu.cn
  • Supported by:
    Project supported by the National Natural Science Foundation of China(21761032);Project supported by the National Natural Science Foundation of China(51363019);the Key Laboratory of Ecological Environment Related Polymer Materials, Ministry of Education Open Fund(KF-18-05)

基于AIE分子和智能响应性聚合物构筑的纳米材料,具有优良的AIE发光性能、环境刺激响应性和生物相容性,已在生命科学领域展现出诱人的应用前景. 本研究通过ATRP活性聚合方法, 以合成的TPE-BIB为引发剂, 引发具有多刺激响应特性的N-[2-(二乙氨基)-乙基]丙烯酰胺单体聚合, 成功制备具有温度/pH/CO2三重响应性的两亲性聚合物: TPE-g-PDEAEAM, 并自组装形成约200 nm的纳米微球. 研究表明: 这种聚合物纳米粒子具有优良的水溶性、单分散性、稳定性及优异的AIE发光特性. 其相转变温度为60 ℃, 溶液荧光对环境温度、pH及CO2均表现出快速敏感响应性能. 同时, 该纳米粒子表现出低细胞毒性, 能够有效示踪HeLa细胞增殖至11代以上, 有望作为一种活细胞荧光示踪探针材料.

关键词: AIE, 多重敏感响应, 聚合物纳米微球, 细胞示踪, 荧光成像

In recent years, fluorescent bioimaging technology has great advantages in the fields of life science research and medical diagnosis because of its advantages of fast and effective, high sensitivity, easy realization of multi-channel imaging and economic efficiency. Organic fluorescent dyes have been widely used as biological imaging reagents due to their excellent photoelectric properties, functional modification, adjustable optical properties, and good biocompatibility. However, conventional organic fluorescent molecules cause aggregation-caused quenching (ACQ) due to π-π stacking in the aggregated state, limiting their bioimaging applications in aggregated or high concentrations. Since the discovery of the unique luminescence phenomenon of aggregation-induced emission (AIE), the ACQ phenomenon of traditional fluorescent materials has been eliminated. Stimulating responsive polymer nanoparticles have been widely used in the life sciences due to their combination of nanoparticle and polymer advantages and their ability to respond intelligently with environmental changes. Therefore, nanomaterials with excellent aggregation-induced emission (AIE) property, environmental stimuli responsiveness and biocompatibility based on AIE molecules and smart responsive polymers have shown attractive application prospects in the life sciences. A kind of multi-responsive AIE-active polymer nanospheres, which were composed of tetraphenylethylene (TPE) and stimuli-responsive poly[N]-2-(diethylamino)-ethyl]acrylamide (PDEAEAM), were constructed in this study. Firstly, a multi-stimulation responsive monomer N-[2-(diethylamino)ethyl]acrylamide (DEAEAM) and TPE derivative tetraphenylethene-4-(12-hydroxydodecyl-2-methylpropionyl) (TPE-BIB) with propionyl bromide were synthesized, respectively, and a multi-stimuli-responsive amphiphilic polymer of tetraphenylethene-graft-poly[N-[2-(diethylamino)ethyl]acrylamide] (TPE-g-PDEAEAM) was then successfully synthesized by atom transfer radical polymerization (ATRP) using TPE-BIB as initiator. Lastly, polymer nanospheres TPE-g-PDEAEAM of approximately 200 nm were formed by a self-assembling pro-cess. The results of the performed experiments showed that the LCST of TPE-g-PDEAEAM in aqueous solution is about 60 ℃. Meanwhile, the luminescence change of TPE-g-PDEAEAM at different temperatures from 20 to 66 ℃ was observed. The fluorescence intensity of TPE-g-PDEAEAM firstly decreased with increasing temperature from 20 to 58 ℃, and the fluorescence intensity increased with increasing temperature from 58 to 66 ℃. The phase transfer of PDEAEAM in TPE-g-PDEAEAM may be the reason of luminescence change which may lead to the fluorescent temperature response. Moreover, the fluorescence intensity of TPE-g-PDEAEAM nanospheres in aqueous solution increased with increasing temperature pH. Besides, the fluorescence intensity of TPE-g-PDEAEAM decreased dramatically when the volume of CO2 increased from 0.0 to 1.2 mL. Therefore, TPE-g-PDEAEAM was a new temperature and pH/CO2 responsive materials and might be used as multi-functional smart fluorescent sensors. More importantly, the fluorescent signals were significantly strong in HeLa cells after cells were incubated with TPE-g-PDEAEAM for 24 h based on the characteristic of AIE fluorescence and low cytotoxicity. The resultant nanospheres were able to be internalized by the cancer cells and effectively track the HeLa cells for as long as 11 passages. So, the polymer nanomaterial is an ideal living cell fluorescent tracer probe, which is expected to be applied as biosensors, long-term cell traces and medical biomaterials.

Key words: AIE, multiple sensitive response, polymer nanospheres, cell tracing, fluorescence imaging