Metal–Organic Frameworks in Raman and SERS: From Chemical Sensing to High-Content Cellular Imaging

Modern cell imaging is increasingly evolving toward high-content, label-free, and spectrally rich analytical approaches capable of resolving biochemical heterogeneity at cellular and subcellular levels. Raman microspectroscopy (µRS) and surface-enhanced Raman scattering (SERS) provide molecularly specific vibrational fingerprints with minimal photobleaching and high multiplexing capability, making them attractive tools for biomedical imaging and cellular analysis. However, broader implementation remains limited by weak intrinsic signals, insufficient targeting specificity, and limited control over nanoscale sensing environments in complex biological systems. Metal–organic framework (MOF) nanoparticles have recently emerged as promising platforms to address these challenges by offering porous, chemically tunable, and structurally well-defined scaffolds for Raman- and SERS-active nanostructures. Their high stability and favourable biocompatibility further support integration into biological applications. This review summarizes recent advances in MOF-assisted µRS and SERS across chemical sensing, bioanalytical detection, and biomedical diagnostics, with particular emphasis on cellular and subcellular imaging. Unlike previous reviews focused primarily on sensing performance, this work highlights the emerging role of MOF-SERS systems in high-content cellular imaging and evaluates their translation toward biologically relevant environments. Key design strategies and current challenges are critically discussed.