Design And Synthesis Of Pancreatic β Cell Targeting System Of Imaging Based On Amphiphilic Polymer

With the increasing of people living standard, diabetes has been a kind of common and frequent disease and onset age becomes younger. It has been a new threat to people health in 21 st century. At present, there are more than 340 million diabetics all over the world. Diabetes brings them huge financial burden and enormous pain. Generally speaking, diabetes is mainly divided into type I diabetes mellitus(T1DM), type II diabetes mellitus(T2DM) and other types such as gestational diabetes mellitus(GDM). Some research shows that no matter type I or type II diabetes, there are both a phenomenon of β cells reduction exist. Therefore, evaluating the β cells mass(BCM) via the imaging methods has very important realistic meaning to the research of diabetes. Throughout various imaging methods, fluorescence imaging is a kind of mature, simple and common method, and NMR imaging favored by most researchers for its excellent spatial resolution as well. However, the contrast agents of the traditional fluorescence imaging are usually semiconductor quantum dots and fluorescent dye which are toxic to cells and unfit for biomedicine use. Also, Gd compound, the contrast agent for T1 NMR imaging is toxic as a kind of heavy metal. Using fluorescence carbon dots to replace fluorescent dye and semiconductor quantum dots and super paramagnetic iron oxide nanoparticles(SPIONPs) to replace Gd compound is a good solution. In this paper, we design and synthesize a kind of biodegradable polymer PIA-g-PEG-g-DDA as a basis, and using glipizide as the target molecule, carbon dots and SPIONPs as the contrast agents to build several kinds of pancreatic β cell targeting nanoparticles of fluorescence and NMR imaging.First, we used itaconic acid to synthesize a kind of multicarboxyl polymer PIA via free radical polymerization. After that, we connected the hydrophilic chain PEG and hydrophobic chain DDA to the main chain via amidation so that we get the amphiphilic polymers PIA-PEG-DDA. Then we conjugated the target molecule glipizide to the main chain through the connective molecule DTPA and amino-terminated PEG to prepare the target molecule modified amphiphilic polymer GLP-PIA-PEG-DDA. Next we used this polymer to encapsulate the SPIONPs so that we get GLP-PIA-PEG-DDA@IOs. TEM and DLS test showed that the nanoparticles are well spherical with a narrow size distribution and the average diameter is 72 nm. Further VSM test proved that GLP-PIA-PEG-DDA@IOs still keeps the superparamagnetism, and exhibits an excellent performance in the NMR imaging test. At last, cytotoxicity test proved it has a low cytotoxicity level.Next the solvothermal method was used to synthesize a kind of novel hydrophobic carbon dots using DDA as passivant and citric acid as the carbon source. It could replace the hydrophobic semiconductor quantum dots in the fluorescence imaging system. A series of optical tests showed that this kind of carbon dots have good features such as a narrow emission spectrum, a small particle size(3nm) and a high quantum yield(30%). Furthermore, it came from carbon materials, which is non-toxic to cells. We used the polymer synthesized previous chapter to capsulate this carbon dots to prepare the β cell targeting fluorescence imaging nanoparticles. The topography test showed that these particles were spherical and the diameter was about 47 nm. Optical tests showed their quantum yield was11.9% and a little red shift in their emission spectrum. So we can affirm it is a perfect fluorescence imaging system. The cell experiment proved the low cytotoxicity and we can believe it could be a kind of fluorescence imaging nanoparticle with high potential.Finally, we changed the synthetic routes using TTDDA as the passivant to prepare a kind of water soluble carbon dots with amino on their surface. These carbon dots have a smaller particle size(<3nm) and the quantum yield is 22%. Using their amino, we connected them to the surface of NMR imaging nanoparticles GLP-PIA-PEG-DDA@IOs and a novel β cell optomagnetic imaging nanoparticles CDs@ GLP-PIA-PEG-DDA@IOs were formation. The polymer served as a bridge between CDs and IOs and played an important role to prevent IOs to quench carbon dots.In conclusion, we used polymer PIA-PEG-DDA as a platform to prepare different pancreatic β cell imaging nanoparticles. Our works could provide new ideas to the study of pancreatic β cells.