Metal-based nanomaterials for laser desorption/ionization mass spectrometry: A frontier for detecting small-molecule biomarkers in coronary artery disease and heart failure

Cardiovascular diseases (CVDs), particularly coronary artery disease (CAD) and heart failure (HF), remain the leading causes of death worldwide. Small-molecule metabolites have emerged as promising biomarkers for early diagnosis and risk stratification, yet their low abundance in complex biological samples such as blood makes accurate detection extremely challenging. Laser desorption/ionization mass spectrometry (LDI-MS) offers a rapid, high-throughput analytical platform, but conventional organic matrices often produce interfering background signals and poor reproducibility, limiting their clinical utility.

A comprehensive review published in LabMed Discovery by researchers from the School of Biomedical Engineering at Shanghai Jiao Tong University and Renji Hospital systematically addresses this bottleneck. Led by Professor Jun Pu, Dr. Yida Huang, and Professor Kun Qian, the team summarizes recent advances in using metal-based nanomaterials as LDI-MS matrices for small-molecule biomarker detection in CAD and HF.

The review provides a clear classification framework based on composition and structural engineering. Regarding composition, the authors discuss single-component systems (noble metals such as gold, silver, platinum, and palladium; and metal oxides such as iron oxide, titanium dioxide, and zinc oxide) as well as multi-component systems (noble metal-based, metal oxide-based, and metal-organic framework (MOF)-based nanocomposites). In terms of structural design, the review covers size and morphology control, porous architectures, core–shell structures, yolk–shell configurations, core–satellite assemblies, and metallic plasmonic arrays. These rationally engineered nanomaterials enhance localized surface plasmon resonance, photothermal conversion, and charge transfer, collectively boosting desorption/ionization efficiency and analytical sensitivity.

Importantly, the review focuses on clinical applications across the entire CAD spectrum, including stable CAD, acute coronary syndrome (ACS), and myocardial infarction (MI), as well as HF. When combined with machine learning algorithms, these nanomaterial-assisted LDI-MS platforms achieve excellent diagnostic performance, with area under the curve (AUC) values exceeding 0.95 for distinguishing disease subtypes, such as unstable angina from acute MI, and ST-segment elevation MI from non-ST-segment elevation MI. The technology also shows promise for differentiating HF from MI combined with HF.

Despite these advances, the authors identify key challenges that must be addressed before clinical translation, including incomplete understanding of the underlying desorption/ionization mechanisms, complex and costly synthesis of functional nanomaterials, and the lack of standardized protocols and multicenter validation. They propose a systematic translational roadmap covering pre-analytical standardization, rigorous quality control of nanomaterials, reliable metabolite identification using high-resolution mass spectrometry, large-scale clinical validation, regulatory engagement, and assessment of cost-effectiveness.

This review offers a valuable reference for researchers in laboratory medicine, nanotechnology, materials science, and analytical chemistry, bridging the gap between advanced nanomaterial design and practical cardiovascular metabolic diagnostics. With continued interdisciplinary collaboration, metal-based nanomaterial-assisted LDI-MS is poised to become a powerful platform for population screening, early diagnosis, and emergency triage in cardiovascular care.