Carbon dots based nanozymes: Synthesis, structure, catalytic mechanisms and applications

Gao et al. [1] discovered that Fe3O4 nanoparticles exhibited peroxidase (POD)-like activity, overturning the traditional belief that inorganic materials are biologically inert. Since then, numerous nanomaterials have been found to mimic enzymes, such as superoxide dismutase (SOD), POD, oxidase (OXD), catalase (CAT) or dehydrogenase, as well as hydrolase, lyase, and isomerase [2]. These findings highlight the biological potential of nanomaterials, establishing nanozymes as a new generation of artificial enzymes. Nanozymes can be categorized into three groups based on composition: metal-based nanozymes (e.g., Pt [3], Au [4], Ni [5] Zn [6], etc.), metal oxide/sulfide-based nanozymes (e.g., Fe3O4 [7], Fe2O3 [8], Mn3O4 [9], etc.), and carbon-based nanozymes (e.g., carbon nanotubes [10], fullerene-like nanostructures [11], carbon dots [12]. While metal oxide/sulfide based nanozymes show promise for biomedical applications, their high cost and potential long-term toxicity limit clinical use [13]. In contrast, carbon-based nanozymes, particularly carbon dots (CDs) based nanozymes, exhibit excellent biocompatibility, low toxicity, and broad applications in cancer therapy, antibacterial treatments, and biosensing [14], [15].

CDs, a star member of carbon-based nanomaterials, are spherical particles less than 10 nm in size with a core-hell structure, encompassing graphene quantum dots (GQDs), carbon quantum dots (CQDs), and carbonized polymer dots (CPDs). Since their discovery in 2004, CDs have attracted widespread attention [16], [17]. In recent years, an increasing number of studies have reported that CDs possess various enzyme-mimicking activities, such as POD, SOD, CAT, and OXD, showing great potential in disease diagnosis, biosensing, imaging, and environmental analysis [18], [19]. Current research has revealed a correlation between the structure of CDs and their enzymatic activities. For instance, doping with different atoms can result in distinct active structures like Fe-N, Cu-N2O2 and Mn-N4/Cu-N4 within CDs [20], [21], [22]. These tailored structures confer higher enzymatic activity and stability upon CDs, which not only overcomes inherent limitations of natural enzyme, such as easy inactivation and challenges in recycling, but also leverages the synergistic effects between the carbon matrix's structure and function to achieve enhanced catalysis. Evidently, through precise structural design and surface modification, the catalytic properties of CDs can be finely tuned to mimic those of natural enzymes, promising broader applications in biotherapy and biosensing [23]. However, the structure-activity relationship of CDs remains inadequately understood, largely due to variations in their raw materials, synthesis and purification methods, and surface structures. Specific challenges include the lack of effective techniques for precisely identifying active sites, a scarcity of systematic studies quantifying the correlation between structural features and catalytic performance, and an incomplete mechanistic understanding of their enzyme-like activities. Therefore, this review summarizes recent advances in CDs exhibiting POD-, SOD-, CAT-, and OXD-like activities, with a focus on their precursors, synthesis and purification methods, sizes, surface functional groups, and heteroatom doping, and how these relate to catalytic mechanisms. We also summarize their latest advances in biotherapy, biosensing, and environmental monitoring (Fig. 1). Finally, we discussed the current challenges and future directions of CDs as novel nanomedicines in clinical translation, aiming to inspire further advances in their rational design and functional deployment.

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