Fluorescence intensity and lifetime imaging of lipofuscin-like autofluorescence for label-free predicting clinical drug response in cancer
Yinghan Yan,
Fuqiang Xing,
Jiayue Cao,
Yiling Hu,
Ling Li,
Zhengyin Gao,
Hao Jia,
Kai Miao,
Fangyuan Shao,
Chu-Xia Deng,
Kathy Qian Luo,
Leo Tsz on Lee,
Tzu-Ming Liu
Affiliations
Yinghan Yan
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China; MOE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
Fuqiang Xing
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China; Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China; Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China; MOE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China; Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
Jiayue Cao
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China
Yiling Hu
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China
Ling Li
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China
Zhengyin Gao
Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China
Hao Jia
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China; MOE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
Kai Miao
Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China; Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China; MOE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China
Fangyuan Shao
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China
Chu-Xia Deng
Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China; Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macau SAR, China; MOE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China; Corresponding author. Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Kathy Qian Luo
Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China; MOE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China; Corresponding author. Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Leo Tsz on Lee
Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China; MOE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China; Corresponding author. Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.
Tzu-Ming Liu
Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China; MOE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, China; Corresponding author. Faculty of Health Sciences, University of Macau, E12 Building, Avenida da Universidade, Taipa, Macau SAR, 999078, China.
Conventional techniques for in vitro cancer drug screening require labor-intensive formalin fixation, paraffin embedding, and dye staining of tumor tissues at fixed endpoints. This way of assessment discards the valuable pharmacodynamic information in live cells over time. Here, we found endogenous lipofuscin-like autofluorescence acutely accumulated in the cell death process. Its unique red autofluorescence could report the apoptosis without labeling and continuously monitor the treatment responses in 3D tumor-culture models. Lifetime imaging of lipofuscin-like red autofluorescence could further distinguish necrosis from apoptosis of cells. Moreover, this endogenous fluorescent marker could visualize the apoptosis in live zebrafish embryos during development. Overall, this study validates that lipofuscin-like autofluorophore is a generic cell death marker. Its characteristic autofluorescence could label-free predict the efficacy of anti-cancer drugs in organoids or animal models.
