Recent progress in nanomaterial-enhanced SALDI-MSI for spatial metabolomics.

Spatial metabolomics enables in situ mapping of metabolites within tissues, which is crucial for understanding physiological and pathological processes, including tumor metabolic reprogramming, neurodegenerative disease mechanisms, and drug distribution in target organs. Mass spectrometry imaging is a powerful tool for spatial metabolomics research. With the advancement of mass spectrometry and nanotechnology, surface-assisted laser desorption/ionization mass spectrometry imaging (SALDI-MSI) that uses nanomaterials instead of organic matrices has emerged, effectively overcoming the inherent limitations of traditional methods in small-molecule metabolite analysis, such as matrix background interference and uneven crystallization. Consequently, SALDI-MSI has become a highly promising analytical technique. This article systematically reviews the latest progress of nanomaterial-enhanced SALDI-MSI in spatial metabolomics. It first introduces various mass spectrometry imaging techniques used in spatial metabolomics, explains their working principles, and compares their advantages and disadvantages. Then, the fundamental mechanisms of SALDI are described to provide a theoretical basis for nanomaterial design, followed by a discussion of common sample preparation methods in SALDI-MSI. The review focuses on the design strategies and application cases of typical nanomaterials for SALDI-MSI, including metal/metal oxide nanoparticles, carbon-based materials, thin-film materials, and nanostructured silicon platforms. Finally, challenges and future directions in standardization, reproducibility, and quantification are discussed. This review aims to provide a reference for the rational design of high-performance SALDI substrates and to promote the development of spatial metabolomics.