Ibrahim Yusuf O, Maalej Nabil, Raja Aamir Younis, Qurashi Ahsanulhaq, Rahmani Mohamed, Venkatachalam Thenmozhi, Abdullah Osama, Paterson Haidee J, Das Gobind, Bradley Curtis C, Nasser Rasha A, Pitsalidis Charalampos
Department of Physics, Khalifa University of Science and Technology, Abu Dhabi, 127788, United Arab Emirates.
Functional Biomaterials Group, Khalifa University of Science and Technology, Abu Dhabi, 127788, United Arab Emirates.
Int J Nanomedicine. 2025 Apr 14;20:4759-4775. doi: 10.2147/IJN.S506187. eCollection 2025.
INTRODUCTION: Recently, diagnostic methods based on multimodal and non-invasive imaging, such as MRI and CT scanners, have been developed for accurate cancer diagnosis. A key limitation of these imaging systems is their low contrast. Therefore, developing stable, non-toxic, and efficient multimodal imaging contrast agents is desirable. In this work, we demonstrated the synthesis of a poly(acrylic acid) (PAA) - coated nanoparticles (NPs), PAA@EuBiGdO-NPs as an imaging agent for contrast enhancement in spectral photon-counting computed tomography (SPCCT), magnetic resonance imaging (MRI) and fluorescence imaging (FL). METHODS: We synthesized PAA-coated EuBiGdO-NPs using a polyol method by dissolving metal nitrates and PAA in triethylene glycol. NaOH solution was added under constant heating at 180°C. The nanoparticles were precipitated with the addition of ethanol, then washed, dried, calcined at 600°C, and redispersed in water for further studies. The nanoparticles were characterized using TEM, SEM, XRD, XPS, FTIR, and PL spectroscopy. PAA@EuBiGdO-NPs were tested in vitro for their cytocompatibility with lung cancer epithelial cells (A549). The nanocomposite image contrast enhancement was evaluated using SPCCT, MRI, and FL imaging. RESULTS: The cell viability study showed that PAA@EuBiGdO-NPs is safe up to 250 µg/mL, exhibiting IC50 values of 365.8 and 337.8 µg/mL after 24 and 48 hours, respectively. The NPs have strong X-ray attenuation with a slope of ~61 HUmL/mg, as determined from the SPCCT concentration-dependent analysis. The MRI of the NPs reveals a high T1 contrast with a relaxivity of 11.77 mMs. Fluorescence imaging of cells incubated with PAA@EuBiGdO₃-NPs shows strong red luminescence. CONCLUSION: The new nanocomposite has proven to be an effective trimodal contrast agent with high attenuation in CT, enhanced T1 signal in MRI, and strong red luminescence in FL imaging with promising diagnostic capabilities.
引言:最近,基于多模态和非侵入性成像的诊断方法,如磁共振成像(MRI)和计算机断层扫描(CT)扫描仪,已被开发用于精确的癌症诊断。这些成像系统的一个关键限制是其对比度较低。因此,开发稳定、无毒且高效的多模态成像造影剂是很有必要的。在这项工作中,我们展示了一种聚(丙烯酸)(PAA)包覆的纳米颗粒(NPs),即PAA@EuBiGdO-NPs作为一种成像剂,用于在光谱光子计数计算机断层扫描(SPCCT)、磁共振成像(MRI)和荧光成像(FL)中增强对比度。 方法:我们通过将金属硝酸盐和PAA溶解在三甘醇中,采用多元醇法合成了PAA包覆的EuBiGdO-NPs。在180°C持续加热下加入NaOH溶液。加入乙醇使纳米颗粒沉淀,然后洗涤、干燥、在600°C煅烧,并重新分散在水中用于进一步研究。使用透射电子显微镜(TEM)、扫描电子显微镜(SEM)、X射线衍射(XRD)、X射线光电子能谱(XPS)、傅里叶变换红外光谱(FTIR)和光致发光(PL)光谱对纳米颗粒进行表征。体外测试了PAA@EuBiGdO-NPs与肺癌上皮细胞(A549)的细胞相容性。使用SPCCT、MRI和FL成像评估了纳米复合材料的图像对比度增强效果。 结果:细胞活力研究表明,PAA@EuBiGdO-NPs在浓度高达250μg/mL时是安全的,在24小时和48小时后的半数抑制浓度(IC50)值分别为365.8和337.8μg/mL。根据SPCCT浓度依赖性分析确定,这些纳米颗粒具有很强的X射线衰减,斜率约为61HUmL/mg。纳米颗粒的MRI显示出高T1对比度,弛豫率为11.77mMs。用PAA@EuBiGdO₃-NPs孵育的细胞的荧光成像显示出强烈的红色发光。 结论:这种新型纳米复合材料已被证明是一种有效的三模态造影剂,在CT中具有高衰减,在MRI中增强T1信号,在FL成像中具有强烈的红色发光,具有很有前景的诊断能力。
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