Accelerating precision anti-cancer therapy by time-lapse and label-free 3D tumor slice culture platform.

Abstract

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.

• Authors: Fuqiang Xing, Yu-Cheng Liu, Shigao Huang, Xueying Lyu, Sek Man Su, Un In Chan, Pei-Chun Wu, Yinghan Yan, Nana Ai, Jianjie Li, Ming Zhao, Barani Kumar Rajendran, Jianlin Liu, Fangyuan Shao, Heng Sun, Tak Kan Choi, Wenli Zhu, Guanghui Luo, Shuiming Liu, De Li Xu, Kin Long Chan, Qi Zhao, Kai Miao, Kathy Qian Luo, Wei Ge, Xiaoling Xu, Guanyu Wang, Tzu-Ming Liu, Chu-Xia Deng
• Journal: Theranostics (Theranostics) Vol. 11 Issue 19 Pg. 9415-9430 ( 2021) ISSN: 1838-7640 [Electronic] Australia
• PMID: 34646378 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The author(s).

Chemical References

• Antineoplastic Agents

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• China
• Drug Discovery (methods)
• Drug Screening Assays, Antitumor (methods)
• High-Throughput Screening Assays (methods)
• Humans
• Mice
• Neoplasms (therapy)
• Optical Imaging (methods)
• Precision Medicine (methods)
• Primary Cell Culture (methods)
• Time-Lapse Imaging (methods)
• Tumor Microenvironment (drug effects)