Role of nanoclusters in the design and development of novel strategies for diagnosis and treatment of infectious diseases.

Despite major advances in sanitation, vaccination, and antimicrobial chemotherapy, infectious diseases continue to pose a huge threat to global health. The ever-increasing occurrences of antimicrobial resistance, emerging pathogens, and persistent diagnostic delays further exacerbate this situation. Over the years, nanotechnology has generated a lot of material platforms to address these failures, and in this study, we critically examine nanoclusters-ultrasmall, atomically precise assemblies (<2 nm cores) with discrete electronic states, as an under-recognized but potentially transformative class of materials for infectious disease diagnostics and therapeutics. Their quantized optical properties, precision ligand chemistry, and unusually high surface-to-volume ratios enable behaviours fundamentally inaccessible to larger nanomaterials, including ratiometric fluorescence reporting, rapid redox-driven antimicrobial activity, and programmable bio-recognition at near-molecular resolution. First, we disentangle NCs from larger nanomaterials by focusing on the consequences of discrete electronic states, ultrasmall hydrodynamic radii, and well-defined ligand shells for transport, clearance, and interactions with pathogens and host-derived biomolecules. Furthermore, the review synthesizes advances in NC-enabled diagnostics, including DNA and aptamer templated Au, Ag, and Cu NC probes, CRISPR/Cas integrated ratiometric sensors, and nanozyme-based readouts that routinely achieve single colony-forming unit or sub-femtomolar detection of bacterial, viral, fungal, and protozoan nucleic acids and antigens. On the therapeutic side, we discuss how the same structural characteristics can be exploited to engineer NCs that mediate controlled ROS generation, membrane and biofilm disruption, quorum sensing interference, photothermal and NIR II photodynamic therapy, and ligand-directed drug delivery, with case studies spanning multidrug-resistant bacteria, opportunistic fungi, and selected parasitic infections. At the same time, we looked at some of the major barriers to clinical translation that remain unaddressed. We show with this study that nanoclusters are not merely "smaller nanoparticles" but a distinct chemical system, capable of enabling modular, multiplexed, and clinically relevant infectious disease interventions. To realize this potential, future work must couple atomic-level design with rigorous pharmacokinetic, toxicodynamic, and translational engineering frameworks.