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조회157

Technical University of Munich

ACS Central Sci., October 21, 2025 | https://doi.org/10.1021/acscentsci.5c01381 A Small Molecule Drug-Based Ru(II) Polypyridine Mass-Tag for Multimodal Imaging of Tissue Samples

Mihyun Park^{1 2}, Melina Rumpf ^{1 2}, Guillermo Moreno-Alcántar ¹, Manuel Seiler ³, Lieby Zborovsky ², Katja Steiger ⁴, Susanne Kossatz ⁵, Angela Casini ^{1 *} and Nicole Strittmatter ^{2 *}

¹Chair of Medicinal and Bioinorganic Chemistry, Department of Chemistry, School of Natural Sciences, Technical University of Munich, 85748 Garching, Germany

²Professorship for Analytical Chemistry, Department of Biosciences, School of Natural Sciences, Technical University of Munich, 85748 Garching, Germany

³Catalysis Research Center Analytic Core Facility, Department of Chemistry, School of Natural Sciences, Technical University of Munich, 85748 Garching, Germany

⁴Comparative Experimental Pathology, Institute of Pathology, School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany

⁵Department of Nuclear Medicine, TUM University Hospital, Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany

^*Corresponding authors: correspondence to Angela Casini or Nicole Strittmatter

Abstract

Mass spectrometry imaging (MSI) is a powerful tool for spatially resolved multiomics analysis of tissue samples in clinical research. However, its proteomics application is still limited due to challenges such as low ionization efficiency and signal interference from complex tissue environments. On-tissue mass-tag labeling (OTMT) addresses these limitations using affinity-based imaging agents that incorporate cleavable, highly ionizable reporter groups known as mass-tags (MTs). The majority of existing MTs rely on antibodies as targeting elements and organic moieties as reporter groups. Here, we introduce a new class of MTs featuring small-molecule inhibitors as binding motifs. Specifically, we present PARPi-MT, composed of a photocleavable and luminescent Ru(II)-based reporter and the poly(ADP-ribose) polymerase (PARP) inhibitor Olaparib for the targeted bimodal imaging of PARP1 in H446 xenograft tumor and mouse brain sections, via desorption electrospray ionization (DESI)-MSI and fluorescence microscopy. Using small-molecule inhibitors as binding motifs expands the design versatility and potential applications of OTMT, while overcoming some of the challenges of antibody-based mass-tags. The Ru(II)-based reporter group offers further advantages, including distinct isotopic signatures derived from the metal center and inherent multimodal imaging capabilities.

논문정보

형식Research article
게재일2025년 10월 (BRIC 등록일 2025-11-04)
연구진국외 연구진
분야 의약학 > 종양의학

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