A High-throughput Microfluidic Platform for Profiling Photosensitizer Efficacy in Cancer Therapeutic Applications.

Drug Screening;Photodynamic Therapy;Microfluidics;Nanoparticle;Photosensitizer;Electrical Engineering;Engineering;Electrical Engineering

Lou, XiaWise, Kensall D. ;

University of Michigan

关键词: Drug Screening;    Photodynamic Therapy;    Microfluidics;    Nanoparticle;    Photosensitizer;    Electrical Engineering;    Engineering;    Electrical Engineering;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/97854/xialou_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

This is a summary of work to develop a high-throughput microfluidic platform for evaluating photodynamic therapy (PDT) efficacy and to investigate its dependence on various therapeutic factors.Evaluating PDT efficacy in vitro is essential in both new photosensitizer development and clinical PDT treatment protocol setup. However, it has been extraordinarily challenging compared to evaluating other anti-cancer drugs due to its extra reliance on light illumination and local oxygen existence. This microfluidic platform exclusively added the microenvironment control of oxygen and light for PDT efficacy evaluation. It provides the capability of comprehensive PDT efficacy response test over various therapeutic factors including photosensitizer concentration, oxygen level, illumination dose (fluence), incubation time and shear stress. A gradient of each therapeutic factor is generated on the chip and by combining these gradients together we can realize a high-throughput efficacy test with various PDT conditions in parallel. So far PDT efficacy under 1,296 different conditions can be evaluated within an active area of 5mmx5mm of one chip in one test run. During the PDT test on chip, each therapeutic factor gradient is confined within a physiologically meaningful range like photosensitizer type1 (Methylene blue concentration (0~10uM), photosensitizer type2 (functionalized nanoparticles) concentration (0~1mg/ml), incubation time (0~75minutes), oxygen level (1.4%~19.1%), illumination dose (0~42.8mJ/cm2) and shear stress (0.75~14.1dyn/cm2). The complete experiment cycle, including both cell culturing in the chip and PDT efficacy test, is restricted within one day providing rapid feedback of test results. PDT efficacy evaluation on the chip has been tested with five kinds of cell lines (C6, 9L, MCF-7, DI TNC1 and Skov3). In general, on chip test result shows an increase in PDT efficacy with photosensitizer concentration, incubation time, oxygen level, illumination dose and a decrease in PDT efficacy with flow shear stress and cancer spheroid size. This ultra-rapid, high-throughput capable microfluidic platform will enable speedy developments of novel photosensitizers, expanding PDT applications in cancer treatments and optimizing clinical PDT protocols. It not only overcomes many limitations of previous technologies for PDT efficacy test, but also can be extensively applied to other anti-cancer drug screening which requires similar investigation on relevant therapeutic factors.