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一种基于天然多糖的 MOF 介导的 Ce6 递药系统,改善了用于光动力治疗的生物性能。

A natural polysaccharide mediated MOF-based Ce6 delivery system with improved biological properties for photodynamic therapy.

机构信息

College of Pharmacy, Pharmaceutical Engineering Research Center, Chongqing Medical University, Chongqing 400016, China.

出版信息

J Mater Chem B. 2020 Feb 21;8(7):1481-1488. doi: 10.1039/c9tb02482d. Epub 2020 Jan 30.

Abstract

Chlorin e6 (Ce6) is a second generation photosensitizer for photodynamic therapy (PDT). However, free Ce6 still has some defects leading to reduced clinical efficacy, such as easy agglomeration in a physiological environment and poor accumulation in tumor tissue. In order to solve these problems, a hyaluronic acid (HA) modified zeolitic imidazolate framework-8 (ZIF-8) based Ce6 (ZIF-8@Ce6-HA) therapeutic agent is constructed for PDT by one-pot encapsulation and self-assembly. ZIF-8@Ce6-HA exhibits acceptable encapsulation efficiency, effective cell uptake and good biocompatibility. Moreover, the results of in vitro anticancer experiments demonstrated that the ZIF-8@Ce6-HA group exhibited greater cytotoxicity after irradiation than the free Ce6 group, which caused about 88.4% of HepG2 cells to die since ROS is produced by PDT. Additionally, the data of inductively coupled plasma mass spectrometry indicated that modification of HA increased the blood circulation time and reduced the systemic toxicity of ZIF-8@Ce6. In summary, this work created an interesting Ce6 therapeutic agent for PDT and provided the data for HA regarding the improvement in biocompatibility and biological half-life of metal organic frameworks.

摘要

叶绿素 E6(Ce6)是第二代光动力疗法(PDT)的光敏剂。然而,游离的 Ce6 仍存在一些缺陷,导致临床疗效降低,例如在生理环境中容易聚集和在肿瘤组织中积累不良。为了解决这些问题,通过一锅封装和自组装,构建了基于透明质酸(HA)修饰的沸石咪唑骨架-8(ZIF-8)的 Ce6(ZIF-8@Ce6-HA)治疗剂,用于 PDT。ZIF-8@Ce6-HA 表现出可接受的包封效率、有效的细胞摄取和良好的生物相容性。此外,体外抗癌实验结果表明,ZIF-8@Ce6-HA 组在照射后表现出比游离 Ce6 组更大的细胞毒性,这导致约 88.4%的 HepG2 细胞死亡,因为 PDT 产生了 ROS。此外,电感耦合等离子体质谱的数据表明,HA 的修饰增加了 ZIF-8@Ce6 的血液循环时间,并降低了其全身毒性。总之,这项工作为 PDT 创造了一种有趣的 Ce6 治疗剂,并提供了关于透明质酸改善金属有机骨架生物相容性和生物半衰期的数据。

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