Toxicity of Carbon Quantum Dots: Is There a Dark Side Beyond Their Brightness?

Carbon quantum dots (CQDs) are a diverse group of carbon nanomaterials that have emerged as promising fluorescent nanomaterials owing to their excellent water solubility, photostability, tunable optical properties, and broad applicability in bioimaging, biosensing, drug delivery, and biomedical applications. Several studies have produced and characterized CQDs using biomass through green chemistry. Despite their widespread application, knowledge regarding their in vivo biosafety remains limited, and most statements regarding good their biocompatibility and low toxicity are based on cell bioassays. To address the limited evidence available on this topic, a systematic literature search was conducted in the Web of Science, Scopus, and PubMed databases, identifying 102 eligible studies published between 2014 and 2026. Hydrothermal synthesis is the predominant production method, with purified water (ultrapure, deionized, double-distilled, or distilled) being the most commonly used solvents. Medicinal plants, fruits, vegetables, agro-industrial residues, and algae are the principal carbon precursors. In vivo results show that different animal models (terrestrial vertebrates, fish, and invertebrate species) generally exhibit excellent biocompatibility, with minimal effects on survival, development, morphology, histopathology, and physiological function after exposure to CQDs. The experimental results also showed biodistribution, persistent fluorescence, and remarkable in vivo imaging performances. Other studies have shown the beneficial effects of CQDs, including wound healing, anti-inflammatory activity, tissue regeneration, neuroprotection, and protection against oxidative stress. Studies on the mechanisms of action induced by CQDs are scarce; however, some studies have analyzed the modulation of oxidative stress, antioxidant activity, and inflammatory responses of CQDs. Even when the evidence collected to date seems to indicate very low toxicity or beneficial effects, the question of how green the green synthesis of CQDs remains open and requires not only more toxicological evidence but also life-cycle analyses.