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钆掺杂碳纳米点作为多模态图像引导光热治疗和肿瘤监测的潜在抗癌工具

Gadolinium-Doped Carbon Nanodots as Potential Anticancer Tools for Multimodal Image-Guided Photothermal Therapy and Tumor Monitoring.

作者信息

Mauro Nicolò, Cillari Roberta, Gagliardo Cesare, Utzeri Mara Andrea, Marrale Maurizio, Cavallaro Gennara

机构信息

Laboratory of Biocompatible Polymers, Department of "Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche" (STEBICEF), University of Palermo, Via Archirafi, 32, 90123 Palermo, Italy.

Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Via del Vespro 129, 90123 Palermo, Italy.

出版信息

ACS Appl Nano Mater. 2023 Sep 5;6(18):17206-17217. doi: 10.1021/acsanm.3c03583. eCollection 2023 Sep 22.

Abstract

This study focuses on the synthesis and characterization of gadolinium-doped carbon nanodots (CDs-Gd) and their potential applications in multimodal imaging and precision cancer therapy. CDs-Gd were synthesized through a solvothermal decomposition method combining citric acid, GdCl, and urea. The incorporation of Gd ions within the carbonaceous structure resulted in stable CDs-Gd with a peculiar architecture that retained optical and paramagnetic properties. Combined characterization techniques confirmed the presence of pH-sensitive COOH functions on the CDs-Gd surface along with the unique lattice structure induced by Gd doping. The optical properties of CDs-Gd exhibited a tunable emission spectrum displaying blue-green emission with pH-dependent behavior. Additionally, CDs-Gd exhibited contrast-enhancing properties in -weighted magnetic resonance imaging (MRI) experiments. MRI acquisitions at different Gd concentrations and pH values demonstrated the potential of CDs-Gd as contrast agents for monitoring pH changes in an aqueous environment. We found that the relaxivity of CDs-Gd at pH 5.5 (tumor, 11.3 mM s) is roughly 3-fold higher than that observed at pH 7.4 (physiological, 5.0 mM s) and outperformed clinical standards such as γ-butyrol (3.3 mM s). Monitoring pH changes in tumor microenvironment (TME) is crucial for evaluating the effectiveness of anticancer treatments and understanding tumor progression. Furthermore, CDs-Gd demonstrated concentration-dependent photothermal conversion ability in the near-infrared (NIR) region, allowing for efficient heat generation under laser irradiation. This indicates the potential application of CDs-Gd in image-guided photothermal therapy (IG-PTT) for cancer treatment. The in vitro studies on MCF-7 (breast cancer) and 16-HBE (healthy bronchial epithelium) cell lines demonstrated that CDs-Gd exhibited high biocompatibility (cell viability >80%). However, upon NIR activation, they showed potent anticancer effects by inhibiting tumor cell proliferation and inducing apoptosis selectively in cancer cells. In conclusion, the synthesized CDs-Gd nanoparticles possess unique optical, photothermal, and MRI contrast properties, making them promising candidates for multimodal imaging-guided precision cancer therapy applications.

摘要

本研究聚焦于钆掺杂碳纳米点(CDs-Gd)的合成与表征及其在多模态成像和精准癌症治疗中的潜在应用。通过将柠檬酸、GdCl和尿素相结合的溶剂热分解法合成了CDs-Gd。钆离子掺入碳质结构中产生了具有独特结构的稳定CDs-Gd,其保留了光学和顺磁性质。联合表征技术证实了CDs-Gd表面存在pH敏感的COOH官能团以及钆掺杂诱导的独特晶格结构。CDs-Gd的光学性质表现出可调谐发射光谱,呈现出与pH相关的蓝绿色发射。此外,在T2加权磁共振成像(MRI)实验中,CDs-Gd表现出对比度增强特性。在不同钆浓度和pH值下进行的MRI采集证明了CDs-Gd作为监测水性环境中pH变化的造影剂的潜力。我们发现,CDs-Gd在pH 5.5(肿瘤,11.3 mM s-1)时的弛豫率比在pH 7.4(生理,5.0 mM s-1)时观察到的弛豫率高出约3倍,并且优于诸如γ-丁内酯(3.3 mM s-1)等临床标准。监测肿瘤微环境(TME)中的pH变化对于评估抗癌治疗的有效性和理解肿瘤进展至关重要。此外,CDs-Gd在近红外(NIR)区域表现出浓度依赖性光热转换能力,能够在激光照射下高效产热。这表明CDs-Gd在用于癌症治疗的图像引导光热疗法(IG-PTT)中具有潜在应用。对MCF-7(乳腺癌)和16-HBE(健康支气管上皮)细胞系的体外研究表明,CDs-Gd表现出高生物相容性(细胞活力>80%)。然而,在近红外激活后,它们通过抑制肿瘤细胞增殖并在癌细胞中选择性诱导凋亡而显示出强大的抗癌作用。总之,合成的CDs-Gd纳米颗粒具有独特的光学、光热和MRI造影特性,使其成为多模态成像引导的精准癌症治疗应用的有前景的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddc/10526686/3430a7548129/an3c03583_0001.jpg

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