Nucleus-targeted carbon dots as peroxidase nanozyme for photoacoustic imaging and phototherapy of tumor

Early accurate diagnosis and precise therapy for cancer are essential to improve the prognosis of patients. Compared with conventional imaging, photoacoustic imaging (PAI) has been widely used as an advanced diagnostic tool in the medical field due to its deep tissue penetration, non-invasive control, high resolution, accuracy and sensitivity [1]. On the other hand, photothermal therapy (PTT) has attracted great attention due to its low side effects, minimal invasiveness, and tumor specific localization [2], [3], [4], [5]. Biocompatible nanoparticles are of great significance for the diagnosis and treatment of tumor. In particular, carbon dots (CDs) or carbon quantum dots (CQDs) with high specific surface area, small size, large π-conjugated structure, good biocompatibility and tunable fluorescence have great application potential in drug carriers, bioimaging and PTT [6], [7], [8], [9].

Current studies of CDs’ imaging mainly focus on fluorescence imaging, however, only a few studies on PAI of CDs were reported [10], [11], [12], [13], [14]. Furthermore, although some advances on PTT of CDs for cancer treatment have been achieved [15], [16], the photothermal conversion efficiency (PCE) of most CDs is still relatively low, as summarized in Table S1 (Supplementary material). To help understand and improve the PCE of CDs, two mechanisms have been proposed, including localized surface plasmon resonance effect and electron-hole generation nuclear relaxation and conjugation or hyperconjugation effect [17]. Recently, several CDs with relatively higher PEC have been reported [18], [19]. For example, Moniruzzaman et al. [18] prepared Y-CQDs with larger polyaromatic sp2 domain and oxidized surface and found that their PCE is 32.6%. Han et al. [19] synthesized CDs with a very high PCE of about 83.7% by solvothermal method using citric acid and urea as raw materials, and dimethyl sulfoxide as solvent. However, the organic raw materials and solvents used in preparation of CDs are not environmentally friendly, and the yield efficiency of CDs is still relatively low [20]. Therefore, it is necessary to take environmental protection and yield efficiency into consideration for the preparation of CDs with PAI and high PCE.

In this work, CDs were prepared by a simple pulse electrolysis method using graphite plates as electrodes in deionized water. Such a preparation method of CDs is pollution-free and environmentally friendly. The yield efficiency of CDs is nearly 100% due to no sample loss during the preparation process. It is found that the current CDs exhibit a high PCE of 64.3% and good PAI property. Subsequently, in vitro cell experiments revealed that CDs have weak inhibition on human normal liver (L-02) cells, while obvious lethality to human hepatoma (HepG2) cells especially under NIR irradiation. Further, the apoptosis-inducing mechanism was revealed by relating to the activity of peroxidase and production of reactive oxygen species. In addition, in vivo biosafety, PAI and PTT of CDs were investigated.

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