首页|金属有机框架纳米材料在PET成像和肿瘤治疗中的应用研究

金属有机框架纳米材料在PET成像和肿瘤治疗中的应用研究

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目的 采用基于正电子发射计算机断层显像(Positron Emission Tomography,PET)成像方式对89Zr-UiO-66/Py-PGA-PEG-F3在肿瘤治疗中的应用进行分析,探究89Zr-UiO-66/Py-PGA-PEG-F3对PET成像和肿瘤治疗的意义.方法 对掺入了正电子发射同位素锆-89(89Zr)的本征放射性UiO-66纳米级金属有机框架(Nanoscale Metal-Organic Frameworks,nMOF)(89Zr-UiO-66)进行合成和分析,89Zr-UiO-66用芘衍生的聚乙二醇(Py-PGA-PEG)进一步功能化,并与F3肽缀合至核仁素,用于靶向三阴性乳腺肿瘤.阿霉素(Doxorubicin,DOX)以相对较高的负载能力(1 mg DOX/mg UiO-66)加载到UiO-66上,并用作治疗性货物和荧光可视化剂.选取3组不同pH值环境验证对DOX释放的影响.结果 功能化的89Zr-UiO-66在不同的生物介质中表现出很强的放射化学和材料稳定性.基于细胞靶向和体内PET成像的发现,89Zr-UiO-66/Py-PGA-PEG-F3、89Zr-UiO-66/Py-PGA-PEG-PEG和89Zr-UiO-66/Py-PGA-PEG-F3+阻断剂量F3肽(10 mg/kg小鼠体重)注射后MDA-MB-231荷瘤小鼠不同时间点的典型冠状位PET图像可以明确核仁素的靶向.结论 89Zr-UiO-66/Py-PGA-PEG-F3可用作PET成像引导、肿瘤选择性货物递送纳米平台.通过将核仁素选择性靶向肿瘤脉管系统和肿瘤细胞,本征放射性的nMOF材料可以在癌症治疗学中得到广泛应用.
Application of Nanoscale Metal-Organic Frameworks(nMOF)in PET and Tumor Therapy
Objective To analyze the application of 89Zr-UiO-66/Py-PGA-PEG-F3 in the treatment of cancer by using positron emission tomography(PET)imaging method,so as to explore the significance of 89Zr-UiO-66/Py-PGA-PEG-F3 in PET imaging and tumor therapy.Methods The intrinsic radioactive UiO-66 nanoscale metal-organic frameworks(nMOF)(89Zr UiO-66)doped with positron emission isotope zirconium-89(89Zr)was synthesized and analyzed.89Zr-UiO-66 was further functionalized with pyrene-derived polyethylene glycol(Py-PGA-PEG)and conjugated with a F3 peptide to nucleolin for targeting of triple-negative breast tumors.Doxorubicin(DOX)was loaded into UiO-66 with a relatively high loading capacity(1 mg DOX/mg UiO-66)and served as both a therapeutic cargo and a fluorescence visualizer.The effects of three different pH values on DOX release were selected.Results Functionalized 89Zr-UiO-66 demonstrated strong radiochemical and material stability in different biological media.Based on the findings of cellular targeting and in vivo PET imaging,the typical coronal PET images of MDA-MB-231 tumor-bearing mice at different time points after injection of 89Zr-UiO-66/Py-PGA-PEG-F3,89Zr-UiO-66/Py-PGA-PEG-PEG and 89Zr-UiO-66/Py-PGA-PEG-F3 + blocking dose F3 peptide(10 mg/kg mouse body weight)could clearly identify the targeting of nucleolin.Conclusion 89Zr-UiO-66/Py-PGA-PEG-F3 can be used as a nanoscale platform for PET imaging guide and tumor selective cargo delivery.By selectively targeting the tumor vasculature and tumor cells with nuclein,this intrinsic radioactive nMOF can be widely used in cancer therapeutics.

nanoscale metal-organic frameworkspositron emission tomographytargeted drug deliverytumor therapy89Zr-UiO-66

魏柯君、薛长国

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安徽理工大学 材料科学与工程学院,安徽 淮南 232001

安徽医科大学附属巢湖医院 物资设备科,安徽 合肥 238000

金属有机框架纳米材料 正电子发射计算机断层显像 靶向给药 肿瘤治疗 89Zr-UiO-66

国家自然科学基金安徽省自然科学杰出青年科学基金安徽省重点研究与开发计划

118720011808085J30202004h07020026

2024

中国医疗设备
中国整形美容协会

中国医疗设备

CSTPCD
影响因子:0.825
ISSN:1674-1633
年,卷(期):2024.39(3)
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