Research Of Targeted Drug Delivery System Based On Nanobody

Cancer is a genetic disease which is a malignant disease that seriously threatens human safety.Cancer is a kind of malignant tumor,the current treatment of cancer is still dominated by chemotherapy.This work describes the design,preparation and test of targeted nanobody-drug conjugates and active-targeted nano-diagnosis and therapy systems.We made an overview about the current research status of Nanobody,including the production,structural features,advantages of application and so on.We designed two works of targeted drug delivery system to better exert the function of tumor inhibition while utilizing the excellent performance of Nanobody with easy modification,high stability and high permeability.The cheap and stable catalytic tools TGase(Transglutaminase)was first used for site-specitific Nanobody PEGylation,with relatively simple operation to obtain high purity PEG antibody.The main work includes two parts:Chapter Ⅱ:Design and preparation of Nanobody-Pt(IV)coupling system.In order to increase the stability of the Nanobody metal drug conjugates,the Nanobody was PEGylated at C-terminal.In case of the smaller molecular size of Nanobody,the PEGylated nanobody could still easy to be cleared during the blood circulation.We synthesized a dendrimeric polylysine with PEG chains as a substrate to prepare a(Nanobody-Pt)4-PEG.Through a series of characterization and functional verification,the(Nanobody-Pt)4-PEG was test to load a certain amount of tetravalent platinum prodrugs with good targeting and tissue permeability.Chapter Ⅲ:Upconversion particles(UCNPs)was produced by thermal decomposition method,and the desolvation method was taken for Human serum albumin(HSA)covered UCNPs.The hydrophobic cavity of HSA loaded the hydrophobic drug doxorubicin.And the sulfur bond of HSA was broken into thiol,and the nanobody was coupled to the surface of the particle by thiol reunion to prepare the targeted diagnosis and treatment system.