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温敏型药物控释系统的构建及光热联合化学疗法协同抗肿瘤作用研究

梁家宁,符开奇,周瑞,叶丽莉,王丽,刘兆敏,孙琳,董妍   

  1. 遵义医科大学珠海校区
  • 收稿日期:2025-03-07 修回日期:2025-04-29 网络首发:2025-05-06 发布日期:2025-05-06
  • 通讯作者: 董妍 E-mail:ydong@zmu.edu.cn
  • 基金资助:
    国家自然科学基金(批准号:31960211, 81960651)、贵州省卫生健康委科学技术基金资助项目(批准号:gzwkj2024-058)和珠海市基础与应用基础课题研究项目(批准号:2320004002780)资助

Construction of Thermosensitive Drug Controlled Release System for Highly Efficient Chemo-Photothermal Tumor Therapy

LIANG Jianing,FU Kaiqi,ZHOU Rui,YE Lili, WANG Li,LIU Zhaomin,SUN Lin,DONG Yan   

  1. Zhuhai Campus of Zunyi Medical University
  • Received:2025-03-07 Revised:2025-04-29 Online First:2025-05-06 Published:2025-05-06
  • Contact: DONG Yan E-mail:ydong@zmu.edu.cn
  • Supported by:
    Supported by the National Natural Science Foundation of China (Nos.31960211,81960651); Science and Technology Foundation of Guizhou Provincial Health Commission(No.gzwkj2024-058); Zhuhai Basic and Applied Basic Research Foundation(No.2320004002780)

摘要: 化疗和热疗联用能有效覆盖整个肿瘤部位,起到协同治疗的效果。本研究以具有独特孔道结构和良好化学稳定性的COFs(DMTP-TAPB)作为壳,光热性质良好的Fe3O4纳米粒作为核,制备粒径约为200 nm的核壳结构药物载体;通过吸附作用将抗肿瘤药物盐酸阿霉素(DOX)封装至COFs孔道内,随后以温敏材料聚N-异丙基丙烯酰胺(PNIPAM)进行修饰,封堵在复合材料表面;进一步的通过808 nm波长的激光照射使Fe?O?纳米粒子迅速将光能转化为热能,进而产生温度变化,一方面,升温使PNIPAM达到临界温度发生相变,其结构向内收缩,从而实现对药物分子的可控释放;另一方面,产生的高温有效的杀灭癌细胞,起到化疗和热疗联用抗肿瘤的效果。最后,在复合材料表面嫁接具有癌细胞主动靶向作用的叶酸碳点,实现叶酸介导的靶向温度响应控释机制,成功的构建了温敏型药物控释系统并联合化学疗法和光热疗法,有效的提升了抗肿瘤效果。

关键词: 共价有机骨架, 纳米载体, 药物递送, 光热联合化学疗法, 抗肿瘤

Abstract: The combination of chemotherapy and photothermal therapy can cover the entire tumor area, achieving a synergistic treatment performance effectively. In this study, COFs (DMTP - TAPB) with a unique pore structure and excellent chemical stability were utilized as the shell, and Fe3O4 nanoparticles with favorable photothermal properties were adopted as the core to construction a core-shell structured drug carrier with a particle size of approximately 200 nm. The antitumor drug doxorubicin hydrochloride (DOX) was encapsulated into the pores of COFs. Subsequently, the composite material was modified with the thermosensitive material poly(N - isopropylacrylamide) (PNIPAM), which was used to seal the surface of the composite. Furthermore, under irradiation with 808 nm laser, Fe3O4 nanoparticles rapidly converted light energy into heat energy, thereby generating a temperature change that achieve two purposes, on the one hand, the temperature change reached the lower critical solution temperature of PNIPAM for phase transition, causing the structure contracts inward and thus achieving the controlled release of drug molecules. On the other hand, the high temperature could kill cancer cells effectively, thus exhibited chemo-photothermal tumor therapy performance. Finally, carbon dots were grafted on the surface of the system to achieve the folic acid-mediated target controlled release mechanism, and a temperature-sensitive drug controlled release system was constructed successfully. The system exhibited highly antitumor performance by combine with chemotherapy and photothermal therapy.

Key words: Covalent organic frameworks, Nanocarrier, Drug delivery, Photothermal combined chemotherapy, Antitumor

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