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