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微流控合成用于 I 型光动力疗法的肿瘤微环境响应型纳系统。

Microfluidic Synthesis of the Tumor Microenvironment-Responsive Nanosystem for Type-I Photodynamic Therapy.

机构信息

Key Laboratory of Artificial Micro and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China.

Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine Southern Medical University, Guangzhou 510515, China.

出版信息

Molecules. 2022 Dec 1;27(23):8386. doi: 10.3390/molecules27238386.

DOI:10.3390/molecules27238386
PMID:36500477
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9736763/
Abstract

Type I photosensitizers with aggregation-induced emission luminogens (AIE-gens) have the ability to generate high levels of reactive oxygen species (ROS), which have a good application prospect in cancer photodynamic therapy (PDT). However, the encapsulation and delivery of AIE molecules are unsatisfactory and seriously affect the efficiency of a practical therapy. Faced with this issue, we synthesized the metal-organic framework (MOF) in one step using the microfluidic integration technology and encapsulated TBP-2 (an AIE molecule) into the MOF to obtain the composite nanomaterial ZT. Material characterization showed that the prepared ZT had stable physical and chemical properties and controllable size and morphology. After being endocytosed by tumor cells, ZT was degraded in response to the acidic tumor microenvironment (TME), and then TBP-2 molecules were released. After stimulation by low-power white light, a large amount of •OH and HO was generated by TBP-2 through type I PDT, thereby achieving a tumor-killing effect. Further in vitro cell experiments showed good biocompatibility of the prepared ZT. To the best of our knowledge, this report is the first on the microfluidic synthesis of multifunctional MOF for type I PDT in response to the TME. Overall, the preparation of ZT by the microfluidic synthesis method provides new insight into cancer therapy.

摘要

具有聚集诱导发光团(AIEgens)的 I 型光敏剂能够产生高水平的活性氧(ROS),在癌症光动力治疗(PDT)中有很好的应用前景。然而,AIE 分子的封装和递送效果并不理想,严重影响了实际治疗的效率。针对这一问题,我们使用微流控集成技术一步合成了金属有机骨架(MOF),并将 TBP-2(一种 AIE 分子)封装到 MOF 中,得到了复合纳米材料 ZT。材料特性表明,所制备的 ZT 具有稳定的物理化学性质和可控的尺寸和形态。ZT 被肿瘤细胞内吞后,会在酸性肿瘤微环境(TME)的作用下降解,然后释放出 TBP-2 分子。在低功率白光的刺激下,TBP-2 通过 I 型 PDT 产生大量的•OH 和 HO,从而达到杀伤肿瘤的效果。进一步的体外细胞实验表明,所制备的 ZT 具有良好的生物相容性。据我们所知,这是第一篇关于针对 TME 的响应型 I 型 PDT 的多功能 MOF 的微流控合成的报告。总的来说,通过微流控合成方法制备 ZT 为癌症治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3940/9736763/e508c286a5d7/molecules-27-08386-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3940/9736763/0beb1b0acec9/molecules-27-08386-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3940/9736763/0b09d0fe982e/molecules-27-08386-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3940/9736763/782cae8d05ff/molecules-27-08386-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3940/9736763/0937a92c104f/molecules-27-08386-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3940/9736763/e508c286a5d7/molecules-27-08386-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3940/9736763/0beb1b0acec9/molecules-27-08386-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3940/9736763/0b09d0fe982e/molecules-27-08386-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3940/9736763/782cae8d05ff/molecules-27-08386-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3940/9736763/0937a92c104f/molecules-27-08386-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3940/9736763/e508c286a5d7/molecules-27-08386-g004.jpg

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