Laboratory of Biocompatible Polymers, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, via Archirafi 32, 90123 Palermo, Italy.
Department of Physics and Chemistry (DiFC) "E. Segrè", University of Palermo, via Archirafi 36, 90123 Palermo, Italy.
ACS Appl Mater Interfaces. 2022 Jan 19;14(2):2551-2563. doi: 10.1021/acsami.1c19599. Epub 2022 Jan 5.
Carbon nanodots (CDs) are a new class of carbon-based nanoparticles endowed with photoluminescence, high specific surface area, and good photothermal conversion, which have spearheaded many breakthroughs in medicine, especially in drug delivery and cancer theranostics. However, the tight control of their structural, optical, and biological properties and the synthesis scale-up have been very difficult so far. Here, we report for the first time an efficient protocol for the one-step synthesis of decagram-scale quantities of N,S-doped CDs with a narrow size distribution, along with a single nanostructure multicolor emission, high near-infrared (NIR) photothermal conversion efficiency, and selective reactive oxygen species (ROS) production in cancer cells. This allows achieving targeted and multimodal cytotoxic effects (, photothermal and oxidative stresses) in cancer cells by applying biocompatible NIR laser sources that can be remotely controlled under the guidance of fluorescence imaging. Hence, our findings open up a range of possibilities for real-world biomedical applications, among which is cancer theranostics. In this work, indocyanine green is used as a bidentate SO donor which has the ability to tune surface groups and emission bands of CDs obtained by solvothermal decomposition of citric acid and urea in ,-dimethylformamide. The co-doping implies various surface states providing transitions in the visible region, thus eliciting a tunable multicolor emission from blue to red and excellent photothermal efficiency in the NIR region useful in bioimaging applications and image-guided anticancer phototherapy. The fluorescence self-tracking capability of SO-CDs reveals that they can enter cancer cells more quickly than healthy cell lines and undergo a different intracellular fate after cell internalization. This could explain why sulfur doping entails pro-oxidative activities by triggering more ROS generation in cancer cells when compared to healthy cell lines. We also find that oxidative stress can be locally enhanced under the effects of a NIR laser at moderate power density (2.5 W cm). Overall, these findings suggest that SO-CDs are endowed with inherent drug-independent cytotoxic effects toward cancer cells, which would be selectively enhanced by external NIR light irradiation and helpful in precision anticancer approaches. Also, this work opens a debate on the role of CD surface engineering in determining nanotoxicity as a function of cell metabolism, thus allowing a rational design of next-generation nanomaterials with targeted anticancer properties.
碳点(CDs)是一类新型的碳基纳米粒子,具有光致发光、高比表面积和良好的光热转换性能,在医学领域,特别是在药物输送和癌症治疗方面取得了许多突破。然而,迄今为止,对其结构、光学和生物性质的严格控制以及合成规模的扩大一直非常困难。在这里,我们首次报道了一种高效的一步法合成数十克数量、具有窄尺寸分布、单一纳米结构多色发射、高光热转换效率和在癌细胞中选择性产生活性氧(ROS)的 N,S 掺杂 CDs 的方法。这使得通过应用近红外(NIR)激光源实现了针对癌细胞的靶向和多模态细胞毒性效应(光热和氧化应激),这些激光源可以在荧光成像指导下进行远程控制。因此,我们的发现为实际的生物医学应用开辟了一系列可能性,其中包括癌症治疗。在这项工作中,吲哚菁绿(ICG)被用作双齿 SO 供体,它能够通过柠檬酸和尿素在二甲基甲酰胺中的溶剂热分解来调节 CDs 的表面基团和发射带。共掺杂意味着各种表面状态提供了可见光区域的跃迁,从而使 CDs 产生从蓝色到红色的可调多色发射,并在生物成像应用和图像引导的抗癌光疗中具有优异的近红外光热效率。SO-CDs 的荧光自追踪能力表明,与健康细胞系相比,它们可以更快地进入癌细胞,并在细胞内化后经历不同的细胞内命运。这可以解释为什么与健康细胞系相比,硫掺杂通过在癌细胞中引发更多的 ROS 生成而导致促氧化活性。我们还发现,在适度功率密度(2.5 W cm)的 NIR 激光作用下,可以局部增强氧化应激。总体而言,这些发现表明,SO-CDs 对癌细胞具有固有、不依赖于药物的细胞毒性作用,这种作用可以通过外部 NIR 光照射选择性增强,并有助于精确的抗癌方法。此外,这项工作引发了关于 CD 表面工程在确定纳米毒性方面的作用的争论,这取决于细胞代谢,从而允许对具有靶向抗癌特性的下一代纳米材料进行合理设计。