Construction Of Gold@Metal-organic Frame Nanocomposites And Their Application For Visualized Theranostics Of Breast Cancer

Breast cancer seriously threatens women's life and health.It is great significant of constructing multi-functional nanoprobes for the safe and efficient theranostics of breast cancer.Nanogold and metal organic framework?MOF?nanomaterials have good biocompatibility and excellent magnetic-optical response characteristics,and can be excellent candidate for multi-functional nanoprobes.In this dissertation,based on the synthesis of nanogold@MOF nanocomposites,ZD2-modified gold nanostar@MOF?AuNS@MOF-ZD2?nanoprobe and doxorubicin?DOX?-carried gold nanoclusters@MOF?AuNCs@MOF-DOX?nanoprobe were respectively constructed,and their performances of magnetic resonance imaging?MRI?/photothermal therapy?PTT?and photodynamic therapy?PDT?/chemotherapy for breast cancer were investigated.The main research contents were as follows:?1?The AuNS@MOF-ZD2 core-shell nanoprobe was constructed to achieve MRI and PTT specifically targeting towards triple negative breast cancer?TNBC?tumor-bearing nude mice.The results showed that AuNS@MOF-ZD2 nanoprobe has well-defined core-shell structure and excellent T₁-weighted MRI performance and photothermal conversion performance.The MR longitudinal relaxation efficiency was 1.2039 mM^-1s^-1,and the photothermal conversion efficiency was up to 40.5%.Under the irradiation of 808 nm laser,the targeted PTT and MRI were realized for TNBC tumor bearing nude mice.Moreover,AuNS@MOF-ZD2 nanoprobe can specifically target TNBC cells?MDA-MB-231?,but not other subtypes of breast cancer cells?MDA-MB-435,MDA-MB-468,and MCF-7?.?2?The AuNCs@MOF-DOX nanoprobe with pH-responsive characteristics was constructed to realize PDT/chemotherapy combination therapy for breast cancer.AuNCs@MOF-DOX nanoprobe showed excellent PDT performance and pH-responsive DOX release,in which PDT performance was attributed to reactive oxygen species?ROS?from AuNCs under 670nm laser irradiation.Under the condition of weak acid,the collapse of MOF structure promoted the release of DOX,and the release rate of DOX was as high as 93.4%.Moreover,under the combination effect of PDT/chemotherapy,the tumor inhibition rate of AuNCs@MOF-DOX nanoprobe was up to 90.1%towards 4T1 tumor-bearing nude mice.