Carbon Dots in Nanomedicine: Advanced Fabrication, Biomedical Applications, and Future Clinical Perspectives

Carbon dots (CDs), including carbon quantum dots (CQDs), are ultra-small carbon-based nanomaterials, typically below 10 nm, with tunable photoluminescence, high aqueous dispersibility, favorable biocompatibility, low toxicity, and abundant surface functional groups. These properties make CDs promising multifunctional platforms for nanomedicine, particularly in bioimaging, biosensing, targeted drug/gene delivery, photodynamic therapy (PDT), photothermal therapy (PTT), antimicrobial treatment, and theranostic applications. This review critically examines recent advances in CD fabrication, including top-down, bottom-up, green biomass-derived, microwave-assisted, hydrothermal, and emerging hybrid strategies, with emphasis on how precursor selection, heteroatom doping, surface passivation, and polymer/ligand functionalization regulate optical performance, biological interaction, and therapeutic efficiency. The review discusses structural classification, including CQDs, graphene quantum dots (GQDs), carbon nanodots, and carbonized polymer dots (CPDs), together with major characterization approaches such as ultraviolet-visible (UV-Vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and high-resolution transmission electron microscopy (HRTEM). Particular attention is given to red/near-infrared (NIR) emission, renal clearance, drug-loading behavior, reactive oxygen species (ROS) generation, toxicity mechanisms, biodistribution, and long-term biosafety. This review also highlights key translational barriers, including batch-to-batch variability, limited standardization, scalable manufacturing, regulatory uncertainty, and incomplete pharmacokinetic evaluation. It considers artificial intelligence (AI) and machine learning (ML) as emerging tools for reproducible CD design. CDs represent versatile and clinically promising nanoplatforms, but their translation requires standardized synthesis, rigorous safety assessment, and application-specific regulatory validation.