Accelerating precision anti-cancer therapy by time-lapse and label-free 3D tumor slice culture platform
| Autor: | Nana Ai, Kathy Qian Luo, Tzu-Ming Liu, Qi Zhao, Pei-Chun Wu, Fuqiang Xing, Wei Ge, Heng Sun, Tak Kan Choi, Kai Miao, Un In Chan, De Li Xu, Shuiming Liu, Ming Zhao, Jianjie Li, Kin Long Chan, Guang-Hui Luo, Sek Man Su, Shigao Huang, Barani Kumar Rajendran, Jianlin Liu, Wenli Zhu, Xueying Lyu, Yinghan Yan, Guanyu Wang, Chu-Xia Deng, Yu-Cheng Liu, Xiaoling Xu, Fangyuan Shao |
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| Rok vydání: | 2021 |
| Předmět: |
Drug
Fluorescence-lifetime imaging microscopy China media_common.quotation_subject Primary Cell Culture Medicine (miscellaneous) Antineoplastic Agents Computational biology Time-Lapse Imaging label-free Efficacy Mice Immune system Cell Line Tumor Neoplasms Drug Discovery Tumor Microenvironment FRET technique Medicine Animals Humans Precision Medicine Pharmacology Toxicology and Pharmaceutics (miscellaneous) media_common Cell Proliferation Drug discovery business.industry Optical Imaging apoptosis personalized medicine Immune checkpoint High-Throughput Screening Assays Autofluorescence Personalized medicine Drug Screening Assays Antitumor business 3D tumor slice culture Research Paper |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | The feasibility of personalized medicine for cancer treatment is largely hampered by costly, labor-intensive and time-consuming models for drug discovery. Herein, establishing new pre-clinical models to tackle these issues for personalized medicine is urgently demanded. Methods: We established a three-dimensional tumor slice culture (3D-TSC) platform incorporating label-free techniques for time-course experiments to predict anti-cancer drug efficacy and validated the 3D-TSC model by multiphoton fluorescence microscopy, RNA sequence analysis, histochemical and histological analysis. Results: Using time-lapse imaging of the apoptotic reporter sensor C3 (C3), we performed cell-based high-throughput drug screening and shortlisted high-efficacy drugs to screen murine and human 3D-TSCs, which validate effective candidates within 7 days of surgery. Histological and RNA sequence analyses demonstrated that 3D-TSCs accurately preserved immune components of the original tumor, which enables the successful achievement of immune checkpoint blockade assays with antibodies against PD-1 and/or PD-L1. Label-free multiphoton fluorescence imaging revealed that 3D-TSCs exhibit lipofuscin autofluorescence features in the time-course monitoring of drug response and efficacy. Conclusion: This technology accelerates precision anti-cancer therapy by providing a cheap, fast, and easy platform for anti-cancer drug discovery. |
| Databáze: | OpenAIRE |
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