Mn₃[Co（CN）₆]₂Nanocube Used As Multi-functional Imaging Contrast Agent And Targeted Drug Delivery

Targeted nanoparticle-based drug delivery and diagnosis is the new trends in current nanobiaomedical research. This smart contrast agent can provide a wide range of clinical information to the early diagnosis of cancer. In the course of treatment, the nano-materials are able to achieve an intuitive observation of whether drugs reach the tumor region and they can monitor the cancer treating process, as well. With the assistant of target element, the nano-material can also help decrease enormous side-effect brought by traditional chemotherapy drugs. Thus, multi-functional nano-materials, which can load, targetly deliver and release drug, have very prominent applications in the fields of cancer diagnosis and treatment.This thesis is mainly focus on the synthesis of core-shell Mn3[Co(CN)6]2@SiO2nanocubes and its application as targeted drug delivery and multi-modal contrast agents. Mn3[Co(CN)6]2nanocubes were synthesized and coated silica onto the surface of the nanocubes to enhace the biocompacitiy. Doxorubicin (DOX) was loaded into the nanocubes and the in-vitro release was envaluated. Targeting element Folate (FA) was conjucted onto Mn3[Co(CN)6]2@SiO2nanocubes and Sprague-Dawley (SD) rats planted brain and subcutaneous C6glioma cells were used to investigate the therapeutic effect in-vivo. The concerns of the dissertation include following aspects:1. Copreciptation method was used to synthesize Mn3[Co(CN)6]2nanocubes and hydrolysis process of tetraethyl orthosilicate was adopted to form core-shell Mn3[Co(CN)6]2@SiO2nanocubes. Mn3[Co(CN)6]2@SiO2exhibited a nanocube shape and were uniform in size (-160nm) and possess a large relative surface area and low cytotocity. This nanocube can be used as contrast agent in MRI and FOI. The Ti relaxation reate of the nanocube is10.52rmV-1s-1and its T2relaxation rate is173.09mM-1s-1, which is sufficient in angiography and brain tumor imaging. In the FOI, the nanocubes can provide signals in the wave-length of403nm and488nm, especially in the two-photon wave-range of720nm.2. Mn3[Co(CN)6]2@SiO2nanocubes are capable to load large amounts of drug, the loading capacity of DOX is818mg/g. During in-vitro real ease process, the nanocubes display a pH response realease phenomenon, which shows a very slow release in pH values lower than7and a repaid release in pH vaules higher than7.3. After being coated the surface of Mn3[Co(CN)6]2@SiO2nanocubes with FA, the DOX loading capacity was increase to869mg/g. Baed on Bio-TEM test, more nanocubes entered into the cell and accumulated in the region of organelles. In in-vivo test, the tumor size of subcutaneous tumor model has decreased obviously during three days of continuous injection of nanocubes and an observation for10days. Further pathology test showed well treating results of the nanocarriers.