Synthesis Of NaGdF₄-based Composite Nanocarriers And Their Applications In Diagnosis And Therapy Of Cancers

Cancers have seriously threatened the health and lives of human beings, and it is greatly significant to develop multimodal or multifunctional contrast agents for the early diagnosis and therapy of cancers. In this dissertation, multifunctional magnetic resonance imaging(MRI) contrast agents based on NaGdF4-based nanocomposite were designed and synthesized, and their applications in diagnosis and therapy of breast cancer were also investigated. The main results were summarized as follows:(1) A multifunctional MRI contrast agent(FA-Gd-Ti NPs) based on folic acid(FA) targeted NaGdF4:Yb/Tm-TiO2 nanocomposites was structured for simultaneously MRI and near infrared(NIR)-responsive inorganic photodynamic therapy(PDT). MTT and H&E staining results indicated that the FA-Gd-Ti NPs had good biocompatibility in vitro and in vivo. MR relaxation and in vivo MRI of MCF-7 tumor-bearing nude mice showed that the nanocomposites were good T1-weighted MRI contrast agents with high longitudinal relaxivity(r1) of 4.53 mM-1 s-1. Under the irradiation of a 980 nm laser at the power density of 0.6 W/cm2 for 20 min, the viabilities of HeLa and MCF-7 cells incubated with FA-Gd-Si-Ti NPs could decrease to 35 % and 31%, respectively. Furthermore, in vivo PDT of MCF-7 tumor-bearing nude mice showed that the inhibition rate of tumors injected with FA-Gd-Si-Ti NPs reached up to 88.6% after 2-week treatment.(2) A multifunctional MRI contrast agent based on doxorubicin(DOX) loaded yolk-shell structured NaGdF4-based nanocarriers was fabriacated for simultaneously MR/upconversion luminescent(UCL) dual-modal imaging and chemotherapy to overcome multidrug resistance of breast cancer. MR measurement indicated that the r1 value of the nanocarriers was 1.04 mM-1 s-1. Under the irradiation of a 980 nm laser, UCL spectra and in vivo UCL imaging of MCF-7/ADR tumor-bearing nude mouse showed the excellent UCL performance of the nanocarriers. Furthermore, the in vitro results of chemotherapy indicated that the uptake of DOX in drug-resistant MCF-7/ADR cells could be improved by nanocarrier delivery, and the efficacy was increased by 11.3% after 24 h incubation compared with free DOX.