Development Of KMnF₃ Nanocrystal As MRI Contrast Agent For Tumor-target Imaging And Therapy

During the past decades, nanomedicine was greatly boosted up, resulting in abundance of diagnosis, therapy techniques. As a typical example, magnetic nanoparticles are being developed as a new type of diagnosis agent for MRI in the past decades, and some of them are on the way to clinical trials. Manganesecontaining nanoparticular contrast agents attracted more and more interest due to its multi-advantage, such as less toxicity, high relaxivity. However, it is still far from the clinic.This master’s thesis dominantly focuns on the development of KMnF3 nanocrystals as MRI contrast agent with high relaxivity and biocompatibility. Three parts are concluded: 1) short cyclic peptide c(RGDyK) was conjugated with carboxylic terminated KMnF3 nanoparticles via EDC coupling and they showed high in vitro bio-stability and biocompatibility. Based on specific bio-recognition between the RGD peptide on the surface of the KMnF3 NPs and integrin aVb3, the application of the c(RGDyK)-conjugated nanoparticles for in vivo MR imaging of tumors profoundly enhanced the image contrast More importantly, the injection dosage required is one to two orders lower than that of a commercial or reported contrast agent. 2) dextran-coated KMnF3 nanocubes, a new type of T1 contrast agent-enhanced magnetic resonance imaging. Through the cellular nanotoxicity tests, such as cell proliferation, oxidative stress and cell membrane integrality, it showed highly biocompatible. Furthermore, when applied in primary liver and metastatic liver cancer of a mouse model, lesions as small as 0.4 mm can be detected. 3) We developed paclitaxel(PTX)-loaded PEGylation KMnF3 NP. The NP has high loading capacity of PTX(0.7 mg PTX/mg Mn ions), enhanced solubility of PTX and high releasing ratio(90%) in the weak acid solution. In Ovarian cancer model, the MRI signal noise ratio of the cancer image increased 170 % as comparison to pre-injection and the tumor growth inhibition effects can be found.In conclusion, based on KMnF3 nanoparticular contrast agent, a series of tasks was carried out. By bioconjugation techniques we synthesized three types of biocompatible contrast agents with targeting groups or anticancer drug coated on the surfaces. To exploring its applied feasibility for early diagnosis, targeted treatment of tumor and drug delivery, the pharmacokinetics were fully characterized as well. Our study illustrated that KMnF3 nanocubes had high biocompatibility, high relaxivity, ease to br decorated, thus hold the promising to clinical application.