响应性透明质酸胶束的合成与性能分析

doi:10.19491/j.issn.1001-9278.2024.07.005

中国塑料 ›› 2024, Vol. 38 ›› Issue (7): 25-31.DOI: 10.19491/j.issn.1001-9278.2024.07.005

响应性透明质酸胶束的合成与性能分析

刘超凡(), 廖盛龙, 仲舒颖, 林英()

安徽工程大学化学与环境工程学院，安徽芜湖 241000

收稿日期:2023-11-21 出版日期:2024-07-26 发布日期:2024-07-24
通讯作者: 林英（1982—），博士，副教授，研究方向为功能高分子设计、组装及应用，liny@ ahpu.edu.cn
E-mail:2604468478@qq.com;liny@ ahpu.edu.cn
作者简介:刘超凡(1998-)，男，在读硕士，研究方向为高分子功能化合成、自组装及应用，2604468478@qq.com
基金资助:
安徽省重点研究与开发计划项目(2022h11020005);安徽省高校优秀科研创新团队项目(2023AH010012)

Synthesis and properties of responsive hyaluronic acid micelles

LIU Chaofan(), LIAO Shenglong, ZHONG Shuying, LIN Ying()

School of Chemical and Environmental Engineering，Anhui Polytechnic University，Wuhu 241000，China

Received:2023-11-21 Online:2024-07-26 Published:2024-07-24
Contact: LIN Ying E-mail:2604468478@qq.com;liny@ ahpu.edu.cn

摘要/Abstract

摘要：

透明质酸（HA）是一种具有癌细胞靶向性的天然多糖，基于特殊功能基团可用于构建病灶环境敏感的高分子纳米载体。本文利用可逆加成⁃断裂链转移（RAFT）聚合可控合成了3⁃丙烯酰胺基苯硼酸与乙烯基吡咯烷酮的嵌段共聚物，通过硼酸酯键与HA自组装形成了纳米胶束。调节两种高分子的投料浓度及优化共聚物的链长比例，能够实现对胶束水合粒径的调控。共聚物浓度为7.5 mg/mL、聚合度为40且嵌段分子量比为2时，组装粒子粒径可以控制在73.3~163.9 nm，有利于体内长循环及病灶渗透。研究表明，该纳米粒子具有良好的pH、糖和盐响应性。合成了多重响应的癌细胞靶向聚合物纳米胶束，具有用作抗肿瘤活性药物及探针载体的潜能。

关键词: 透明质酸, 3?丙烯酰胺基苯硼酸, 嵌段共聚, 响应性, 纳米胶束

Abstract:

Hyaluronic acid （HA） is a natural polysaccharide with cancer cell targeting properties， and it can be used to construct polymeric nanocarriers sensitive to lesion environments based on special functional groups. Herein， the reversible addition⁃fragmentation chain transfer （RAFT） polymerization was used to synthesize a block copolymer of 3⁃acrylamide phenylboronic acid and vinyl pyrrolidone controllably. This block copolymer was self⁃assembled with hyaluronic acid through the borate ester bond to form nano⁃micelles. Adjusting the feeding concentration of two types of polymers and optimizing the chain length ratio of copolymers can obtain the regulation of micellar hydrodynamic diameter. When the concentration of copolymer was 7.5 mg/mL， the degree of polymerization was 40 and the molecular weight ratio of block was 2. The obtained particle size could be tunable from 73.3 to 163.9 nm， which is advantageous to long circulation in vivo and lesion penetration. The findings indicated that the nanoparticles had suitable pH， sugar， and salt responsiveness. In summary， a multi⁃responsive cancer cell targeting polymer nano⁃micelle has been synthesized in this study， and it exhibits great potential for applications as an antitumor drug and probe carrier.

Key words: hyaluronic acid, 3?acrylamide phenyl boronic acid, block copolymerization, responsiveness, nano micelle

中图分类号:

TQ320

刘超凡, 廖盛龙, 仲舒颖, 林英. 响应性透明质酸胶束的合成与性能分析[J]. 中国塑料, 2024, 38(7): 25-31.

LIU Chaofan, LIAO Shenglong, ZHONG Shuying, LIN Ying. Synthesis and properties of responsive hyaluronic acid micelles[J]. China Plastics, 2024, 38(7): 25-31.

图/表 11

图1 PAPBA⁃b⁃PVP/HA胶束的制备路线

Fig.1 Schematic of the preparation of PAPBA⁃b⁃PVP/HA micelles

图2 APBA和PAPBA的1H⁃NMR和FTIR谱图以及PAPBA的GPC曲线

Fig.2 1H⁃NMR and FTIR spectra of APBA and PAPBA， as well as GPC curves of PAPBA

图3 PAPBA⁃b⁃PVP 的1H⁃NMR谱图以及PAPBA⁃b⁃PVP、NVP和PAPBA的FTIR谱图

Fig.3 1H⁃NMR spectra of PAPBA⁃b⁃PVP and FTIR spectra of PAPBA⁃b⁃PVP， NVP and PAPBA

图4 PAPBA⁃b⁃PVP的GPC曲线

Fig 4 GPC curves of PAPBA⁃b⁃PVP

图5 不同HA浓度调控的PAPBA⁃b⁃PVP/HA胶束照片和HA、PAPBA⁃b⁃PVP和PAPBA⁃b⁃PVP/HA的FTIR谱图

Fig.5 Photo of PAPBA⁃b⁃PVP/HA micelles regulated by different HA concentrations and FTIR of HA， PAPBA⁃b⁃PVP and PAPBA⁃b⁃PVP/HA

图6 粒径为142 nm与156.2 nm胶束的SEM照片和水合粒径分布图

Fig.6 Images and hydrodynamic diameter distribution of micelles with particle size of 142 nm and 156.2 nm，respectively

图7 共聚物嵌段比、投料浓度与HA浓度对胶束水合粒径的调控

Fig.7 Hydrodynamic diameter changes of micelles with different block ratios and feed concentrations of the copolymer as a function of HA concentration

图8 共聚物和HA的投料浓度对胶束粒径的影响以及3 mg/mL HA下，共聚物浓度对胶束粒径与Zeta电位的影响

Fig.8 Effect of concentrations of reactants on the size of micelles and effect of the copolymer concentrations on micelle particle size and zeta potential at 3 mg/mL HA

图9 纳米胶束在介质中的胶体稳定性

Fig.9 Colloidal stability of nano micelles in media

图10 pH值对纳米胶束粒径及Zeta电位的影响

Fig.10 The diameters and zeta potentials of nano micelles at different pH values

图11 葡萄糖和NaCl浓度对胶束粒径的影响以及胶束的糖和盐响应作用机理

Fig.11 Effect of glucose and salt concentrations on the size of micelles and the sugar and salt responsive mechanism of micelles

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响应性透明质酸胶束的合成与性能分析

Synthesis and properties of responsive hyaluronic acid micelles

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