基于单线态氧荧光传感的微流控光动力疗法研究  

Microfluidic Photodynamic Therapy Based on Singlet Oxygen Fluorescence Sensing

作　　者：孙煜然 彭洪尚[1] SUN Yuran;PENG hongshang(School of Science,Minzu University of China,Beijing 100081,China)

机构地区：[1]中央民族大学理学院,北京100081

出　　处：《发光学报》2024年第9期1560-1567,共8页Chinese Journal of Luminescence

基　　金：国家自然科学基金(62175266)。

摘　　要：光动力疗法(PDT)作为一种新型的光疗技术,具有非侵入性和毒副作用小的优点,在临床医学上具有重要的应用前景。目前PDT研究主要基于静态培养的肿瘤细胞,其与实际肿瘤微环境差异明显因而往往导致PDT临床疗效不佳。本文设计开发一种微流控生物芯片用于肿瘤PDT,并制备荧光纳米传感器(λex=410 nm,λem=460 nm)对PDT过程单线态氧的产生进行荧光传感,分析影响PDT灭活肿瘤细胞的主要因素。结果表明,培养基pH由7.4减小至6.8(环境酸化)以及注射流量由5μL/h增加到20μL/h(剪切应力增大)均会降低肿瘤细胞对纳米光敏剂的吞噬效率;PDT初期氧含量充足(<30 s),光敏药物剂量、微酸化和力学微环境的差异对单线态氧的产率影响不大,细胞抑制率接近;PDT后期(30~180 s)氧含量下降,单线态氧产率下降,不同的肿瘤微环境参量产生的细胞光毒性差异明显。该工作通过荧光传感探究了模拟肿瘤微环境下PDT过程中单线态氧的产生情况,为推进肿瘤PDT的临床发展提供了有益的参考。Photodynamic therapy(PDT),as a new type of phototherapy technology,has the advantages of non-inva-sive and low toxic side effects,and has important application prospects in clinical medicine.Currently,PDT research is mainly based on statically cultured tumor cells,which significantly differ from the actual tumor microenvironment and often lead to poor clinical efficacy of PDT.This paper designs and develops a microfluidic biochip for tumor PDT,and prepares a fluorescent nanosensor(λex=410 nm,λem=460 nm)to fluorescently sense the production of singlet oxygen during the PDT process,analyzing the main factors affecting the inactivation of tumor cells by PDT.The results show that reducing the pH of the culture medium from 7.4 to 6.8(environmental acidification)and increasing the injection flow rate from 5μL/h to 20μL/h(increased shear stress)both reduce the phagocytic efficiency of tumor cells towards nano photosensitizers.In the early stage of PDT,the oxygen content is sufficient(<30 s),and the differences in photo-sensitizer dosage,microacidification,and mechanical microenvironment have little effect on the yield of singlet oxy-gen.The cell phototoxicity is similar.In the late stage of PDT(30-180 s),the oxygen content decreases,the yield of singlet oxygen decreases,and different tumor microenvironment parameters result in different cellular phototoxicity.This work explores the production of singlet oxygen during PDT in a simulated tumor microenvironment through fluores-cence sensing,providing useful references for promoting the clinical development of tumor PDT.

关 键 词：荧光传感 单线态氧 微流控芯片 光动力疗法 

分 类 号：O482.31[理学—固体物理]