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材料导报  2024, Vol. 38 Issue (14): 23020219-6    https://doi.org/10.11896/cldb.23020219
  高分子与聚合物基复合材料 |
交联诱导重组装多重刺激响应型聚合物胶束的制备及抗肿瘤应用
唐昭敏*, 赵健清, 周建仁, 唐婉兰, 魏佳元, 韩秉锟, 吕文轩
西南石油大学新能源与材料学院,成都 610500
Preparation and Anticancer Application of Crosslink-induced Reassembly and Multiple-stimulus Responsive Polymer Micelles
TANG Zhaomin*, ZHAO Jianqing, ZHOU Jianren, TANG Wanlan, WEI Jiayuan, HAN Bingkun, LYU Wenxuan
School of New Energy and Materials, Southwest Petroleum University, Chengdu 610500, China
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摘要 本工作合成了基于聚赖氨酸的三嵌段两亲性聚合物mPEG-P(LL/LL-LA)-PCL-IR820,其中聚赖氨酸链为交联剂硫辛酸(LA)提供了反应位点,疏水链段的聚己内酯(PCL)为物理包埋化疗药物阿霉素(DOX)提供了可行性。随后,光敏剂(IR820)通过酯键接枝到PCL上得到mPEG-P(LL/LL-LA)-PCL-IR820。将聚合物通过溶剂蒸发法制备未交联载药胶束(DUCM),再使用交联诱导剂二硫苏糖醇(DTT)诱导LA制备交联载药胶束(DCM)。由于内部交联结构的存在,DCM在经历注射和血液循环后保持结构稳定,并且在进入肿瘤细胞后,LA中的二硫键会在肿瘤细胞中高浓度谷胱甘肽(GSH)作用下断裂,从而释放化疗药物,避免了未交联胶束因剪切力和蛋白质吸附作用而提前裂解,进而避免了药物在体内的非特异性分布。最终,该交联纳米胶束协同化疗和光动力疗法高效杀死癌细胞,为胶束在药物传递系统中的研发提供了有价值的参考。
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唐昭敏
赵健清
周建仁
唐婉兰
魏佳元
韩秉锟
吕文轩
关键词:  交联诱导  胶束  光疗  协同治疗  多重刺激响应    
Abstract: This work synthesized a three-block amphiphilic polymers mPEG-P(LL/LL-LA)-PCL-IR820 based on polylysine, in which lysine chain provided reaction sitesfor cross-linking reagent maleic anhydride (LA), and the hydrophobic chain segment polycaprolactone (PCL) provided feasibility for physical encapsulation of anticancer drug doxorubicin (DOX). Subsequently, the photosensitizer IR820 was grafted onto PCL to obtain mPEG-P(LL/LL-LA)-PCL-IR820 via ester bonding. The drug-loaded un-crosslinked micelles (DUCM) were fabricated by solvent evaporation method, and the drug-loaded crosslinked micelles (DCM) were prepared through LA crosslinking induced by the cross-linking inducer dithiothreitol (DTT). Due to the internal crosslinking structure, DCM remained stable after injection and blood circulation. Once entering the tumor cells, the disulfide bond in LA broke down under high concentration of glutathione (GSH) in tumor cells and DOX was rapidly released, which avoided the premature degradation of the uncrosslinked micelles (DUCM) induced by the shear force and protein adsorption and the non-specific distribution of the drug in the body. As a result, the crosslinked micelles showed excellent cytotoxicity to cancer cells combined chemotherapy with photodynamic therapy, which is a promising research in drug delivery system.
Key words:  crosslink-induced    micelle    phototherapy    synergistic therapy    multiple-stimulus response
出版日期:  2024-07-25      发布日期:  2024-08-12
ZTFLH:  R730.53  
基金资助: 国家自然科学基金青年基金(51803174);四川省科学技术厅青年基金(2024NSFSC0988)
通讯作者:  * 唐昭敏,西南石油大学新能源与材料学院高级实验师,博士,硕士研究生导师。主要从事新型功能纳米材料在抗肿瘤方面的研究。作为课题组负责人主持国家自然科学基金青年基金和四川省科技厅青年基金,以第一作者及通信作者在Biomaterials、Advanced Healthcare Materials、Acta Biomaterialia、Separation and Purification、Microporous and Mesoporous Materials、Molecular Pharmaceutics、European Journal of Pharmaceutics and Biopharmaceutics等高水平期刊上发表多篇SCI论文。tl8687@163.com   
引用本文:    
唐昭敏, 赵健清, 周建仁, 唐婉兰, 魏佳元, 韩秉锟, 吕文轩. 交联诱导重组装多重刺激响应型聚合物胶束的制备及抗肿瘤应用[J]. 材料导报, 2024, 38(14): 23020219-6.
TANG Zhaomin, ZHAO Jianqing, ZHOU Jianren, TANG Wanlan, WEI Jiayuan, HAN Bingkun, LYU Wenxuan. Preparation and Anticancer Application of Crosslink-induced Reassembly and Multiple-stimulus Responsive Polymer Micelles. Materials Reports, 2024, 38(14): 23020219-6.
链接本文:  
http://www.mater-rep.com/CN/10.11896/cldb.23020219  或          http://www.mater-rep.com/CN/Y2024/V38/I14/23020219
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