Metal-doped and hybrid carbon dots: A comprehensive review on their synthesis and biomedical applications.

Carbon dots (CDs) are the most promising candidates of the carbon family with superior properties like ultra-small size, high aqueous solubility, low cytotoxicity, and inherent photoluminescence which makes them suitable for diverse biomedical applications. Methods have been developed to enhance their applications. Doping/surface passivation of CDs improves their physicochemical properties, visible light absorption probability, and quantum yield by controlling their size, morphology, structure, and band-gap energy. Recently, metal-doped CDs have emerged as an important class of nanomaterials with numerous biomedical applications. Additionally, the conjugation of CDs with semiconductor metal-oxide nanoparticles (NPs) enhances their free radical production rates under visible light irradiation. Conjugation of fluorescent CDs with magnetic NPs leads to the development of multimodal imaging platforms. Similarly, ternary conjugates composed of fluorescent CDs, near-infrared (NIR) responsive, and magnetic NPs are useful for multi-modal imaging-guided, and NIR-responsive synergistic chemo-phototherapy. However, no comprehensive review is published yet which covers metal-doped and hybrid CDs. Therefore, herein we provide detailed information about their synthesis and important biomedical applications. Firstly, we have covered various synthesis methods for CD conjugation including the critical analysis of the effects of the reaction conditions and doping/conjugation on the structure and properties of the CDs. Then we have extensively reviewed their biomedical applications as antimicrobial, antioxidant, and bioimaging agents, and in the field of cancer phototherapy with special emphasis on their mechanisms of actions. Finally, the future directions of research and the applications of the metal-doped and hybrid CDs have been discussed. We believe that this review article will enrich the understanding of different synthetic routes of CD-nanocomposites and their biomedical applications.