Tedeschi Giulia, Palomba Francesco, Scipioni Lorenzo, Digman Michelle A
Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, Irvine, California 92617, United States.
Beckman Laser Institute, University of California, Irvine, Irvine, California 92617, United States.
Chem Biomed Imaging. 2025 May 15;3(7):433-442. doi: 10.1021/cbmi.5c00021. eCollection 2025 Jul 28.
We implemented a multimodal set of functional imaging techniques optimized for deep-tissue imaging to investigate how cancer cells invade surrounding tissues and how their physiological properties change in the process. As a model for cancer invasion of the extracellular matrix, we created 3D spheroids from triple-negative breast cancer cells (MDA-MB-231) and nontumorigenic breast epithelial cells (MCF-10A). We analyzed multiple hallmarks of cancer within the same spheroid by combining a number of imaging techniques, such as metabolic imaging of nicotinamide adenine dinucleotide by fluorescence lifetime imaging microscopy (NADH-FLIM), hyperspectral imaging of a solvatochromic lipophilic dye (Nile Red), and extracellular matrix imaging by second harmonic generation (SHG). We included phasor-based bioimage analysis of spheroids at three different time points, tracking both morphological and biological properties, including cellular metabolism, fatty acid storage, and collagen organization. Employing this multimodal deep-imaging framework, we observed and quantified cancer cell plasticity in response to changes in the environment composition.
我们实施了一套针对深部组织成像进行优化的多模态功能成像技术，以研究癌细胞如何侵入周围组织以及它们在这个过程中的生理特性如何变化。作为癌细胞侵袭细胞外基质的模型，我们用三阴性乳腺癌细胞（MDA-MB-231）和非致瘤性乳腺上皮细胞（MCF-10A）创建了三维球体。我们通过结合多种成像技术，如利用荧光寿命成像显微镜对烟酰胺腺嘌呤二核苷酸进行代谢成像（NADH-FLIM）、对溶剂化显色亲脂性染料（尼罗红）进行高光谱成像以及通过二次谐波产生进行细胞外基质成像（SHG），在同一个球体中分析了癌症的多个特征。我们在三个不同时间点对球体进行了基于相量的生物图像分析，追踪形态学和生物学特性，包括细胞代谢、脂肪酸储存和胶原蛋白组织。利用这个多模态深度成像框架，我们观察并量化了癌细胞对环境组成变化的可塑性。
