Gasparin Francesca, Tietje Marlene R, Katab Eslam, Nurdinova Aizada, Yuan Tao, Chmyrov Andriy, Uluç Nasire, Jüstel Dominik, Bassermann Florian, Ntziachristos Vasilis, Pleitez Miguel A
Institute of Biological and Medical Imaging, Helmholtz Zentrum München, Neuherberg, Germany.
Chair of Biological Imaging at the Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health, Technical University of Munich, Munich, Germany.
Nat Biomed Eng. 2025 Jul 14. doi: 10.1038/s41551-025-01443-3.
The efficacy of drug therapy in multiple myeloma is conventionally assessed by whole-cell-population methods, serum analysis of light chains and monoclonal antibodies, immunofixation electrophoresis, or by flow cytometry of bone marrow aspirates and biopsies. These methods provide relevant information on the presence of specific immunoglobulins at high sensitivity and specificity but require a large number of cells, involve long and laborious sample preparation steps, and provide only tumour bulk information. Here we develop a single-cell imaging technique requiring a reduced number of primary cells for longitudinal evaluation of patient-specific treatment and assessment of treatment heterogeneity. By exploiting the mechanistic action of proteasome inhibition and in synergy with the label-free protein-structure specificity of mid-infrared optoacoustic microscopy, we present a technology that facilitates longitudinal evaluation of myeloma treatment and a patient's heterogeneous response. Detecting optical-generated ultrasound waves that intensify with optical absorption, this technology allows observation of proteins in living cells with high sensitivity. Specifically, we use intermolecular β-sheet formation as a biomarker for cell viability during therapy and apply it to assess drug-treatment performance in multiple myeloma patients.
传统上，多发性骨髓瘤的药物治疗疗效是通过全细胞群体方法、轻链血清分析和单克隆抗体、免疫固定电泳，或通过骨髓穿刺液和活检的流式细胞术来评估的。这些方法在高灵敏度和特异性方面提供了关于特定免疫球蛋白存在的相关信息，但需要大量细胞，涉及冗长且费力的样品制备步骤，并且仅提供肿瘤体积信息。在此，我们开发了一种单细胞成像技术，该技术需要较少数量的原代细胞来对患者特异性治疗进行纵向评估并评估治疗异质性。通过利用蛋白酶体抑制的作用机制，并与中红外光声显微镜的无标记蛋白质结构特异性协同作用，我们提出了一种有助于对骨髓瘤治疗和患者异质性反应进行纵向评估的技术。该技术通过检测随光吸收增强的光生超声波，能够以高灵敏度观察活细胞中的蛋白质。具体而言，我们将分子间β-折叠的形成用作治疗期间细胞活力的生物标志物，并将其应用于评估多发性骨髓瘤患者的药物治疗效果。
