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材料导报  2023, Vol. 37 Issue (20): 22040099-6    https://doi.org/10.11896/cldb.22040099
  高分子与聚合物基复合材料 |
叶酸修饰的金属有机配位聚合物用于肿瘤靶向及化学/光热协同治疗
黄道远, 谢德明*
暨南大学生命科学技术学院,广州 510000
Folate-modified Metal-Organic Coordination Polymers for Tumor Targeting and Chemo/Photothermal Synergistic Therapy
HUANG Daoyuan, XIE Deming*
College of Life Science and Technology, Jinan University, Guangzhou 510000, China
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摘要 将光热疗法(PTT)与化学疗法相结合,通过精确控制药物释放,降低多药耐药性,提高治疗效果,已成为乳腺癌治疗的一种有前景的策略。为此本工作设计制备了基于小分子抗肿瘤药物槲皮素的金属-有机配位纳米递送体系FA-PEG/Qu-Fe(Ⅱ)-PDA(FA@QFD NPs),并将其用于肿瘤靶向及化学/光热协同治疗。通过“一锅法”将槲皮素、盐酸多巴胺和亚铁离子共混配位合成了Qu-Fe(Ⅱ)-PDA(QFD NPs),进一步使用FA-PEG-NH2进行靶向修饰,得到了FA@QFD NPs。该配位体系实现了槲皮素高达31.61%的载药量和95.1%的药物包封率,有效地改善了槲皮素水溶性差、药物利用率低的缺陷。该纳米体系在正常生理环境下表现出良好的稳定性,并能通过叶酸靶向肿瘤细胞,在肿瘤微环境较低的pH值以及丰富的过氧化氢作用下导致配位键断裂,释放槲皮素进行化疗,同时在红外光照射下聚多巴胺(PDA)产生光热效应进一步杀伤肿瘤细胞。将FA@QFD NPs与4T1细胞孵育,在808 nm激光照射下,癌细胞的平均存活率仅为14.73%,远低于单一治疗组的62.48%。本工作不仅设计了一种用于化学/光热协同治疗的高效抗癌纳米粒子,也为那些水溶性差的多酚类药物的负载提供了一种新策略。
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黄道远
谢德明
关键词:  化疗  光热治疗  肿瘤靶向  金属有机配位物  槲皮素    
Abstract: Photothermal therapy (PTT) combined with chemotherapy has become a promising strategy for breast cancer treatment by precisely controlling drug release, reducing multidrug resistance and improving therapeutic efficacy. To this end, we designed and prepared a metal-organic coordination nano-delivery system FA-PEG/Qu-Fe(II)-PDA (FA@QFD NPs) based on the small molecule antitumor drug quercetin for tumor targeting chemistry/photothermal synergistic therapy. First, QFD NPs were synthesized from quercetin, dopamine hydrochloride and ferrous ion by ‘one-pot’ method, and then targeted modification with FA-PEG-NH2 was carried out to obtain FA@QFD NPs. The coordination system achieves the drug loading of quercetin as high as 31.61% and the drug encapsulation efficiency of 95.1%, which effectively improves the defects of poor water solubility and low drug utilization rate of quercetin. The nano system exhibits good stability under normal physiological environment, and can target tumor cells through folic acid, which leads to the cleavage of coordination bonds under the action of low pH value and abundant hydrogen peroxide in the tumor microenvironment, releasing quercetin for chemotherapy, and further killing tumor cells can be enhanced under infrared irradiation and photothermal effect generated by polydopamine (PDA). When FA@QFD NPs were incubated with 4T1 cells, the average survival rate of cancer cells under 808 nm laser irradiation was only 14.73%, which was much lower than the 62.48% in the monotherapy group. This work not only designs a highly efficient anticancer nanoparticle for chemical/photothermal synergistic therapy, but also provides a new idea for the loading of those poorly water-soluble polyphenols.
Key words:  chemotherapy    photothermal therapy    tumor targeting    metal-organic complexes    quercetin
出版日期:  2023-10-25      发布日期:  2023-10-19
ZTFLH:  R730.53  
通讯作者:  *谢德明,暨南大学生物医学工程研究所副教授、硕士研究生导师。1998年华南理工大学食品与生物工程学院博士毕业,1998年暨南大学生物医学工程研究所工作至今。目前主要从事医用高分子材料与医疗器械、生物降解高分子材料等方面的研究与应用开发工作。发表论文40余篇,包括Nanoscale、Biomedical Materials、 Journal of Biomaterials Science-Polymer Edition、 Biomedical and Environmental Sciences、 Materials Science and Engineering C、 RSC Advances等,获得发明专利授权11项,出版《生物医学工程学进展》。承担包括国家自然科学基金项目等20余项。bme2004@126.com   
作者简介:  黄道远,2019年6月毕业于湖南工程学院,获得工学学士学位。现为暨南大学生命科学技术学院硕士研究生,在谢德明教授的指导下进行研究。主要研究方向为生物医用材料。
引用本文:    
黄道远, 谢德明. 叶酸修饰的金属有机配位聚合物用于肿瘤靶向及化学/光热协同治疗[J]. 材料导报, 2023, 37(20): 22040099-6.
HUANG Daoyuan, XIE Deming. Folate-modified Metal-Organic Coordination Polymers for Tumor Targeting and Chemo/Photothermal Synergistic Therapy. Materials Reports, 2023, 37(20): 22040099-6.
链接本文:  
http://www.mater-rep.com/CN/10.11896/cldb.22040099  或          http://www.mater-rep.com/CN/Y2023/V37/I20/22040099
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