Synthesis Of Novel Nanoparticles With Antifouling Property And Their Biomedical Applications

During the application process of biosensors,implanted medical devices,targeted drug/gene delivery carriers,tissue scaffolds,targeted molecular imaging probes,Immunodiagnostic reagents,etc.nonspecific adsorption of biomolecules like protein and DNA would damage their performance.For example,nonspecific adsorption of proteins to implanted biomaterials will deactivate the surface functional groups,decrease the sensitivity of biosensors,or lead to increase of background detection signal,even appearance of false positive results.Therefore,synthesis of antifouling materials and study of their antifouling properties turn to be one of the research hotpots in functional materials in recent years.Reducing the adhesion of non-specific proteins and biomolecules to the surfaces of nanoparticles has long been a goal of biomedical engineering.An efficient approach is the surface modification of biomaterials with polymeric and low-weight molecules coatings to make them antifouling with regard to body fluids and the surrounding tissue.on the basis of previous researches,this thesis focused on the synthesis of novel nanoparticles with antifouling property,interaction with protein,and application in biomedical feild.In chapter two,on the basis of many years researches in our lab,we found the ultrasmall superparamagnetic iron oxide?USPIO?nanoparticles coated with poly?acrylic acid??PAA@USPIOs?owned high stability and antifouling property in physiological conditions which means a great potential for MRI contrast agent.The druggability of PAA@USPIOs have be systematically studied including toxicity,efficacy and drug metabolism.Our study indicated that the PAA@USPIOs with the potential to be developed into a MRI contrast agent for future clinical application.In chapter three,a novel surface-initiated RAFT polymerization?SI-RAFT?route was designed to synthesize SiO₂@pCBMA.The zwitterionic spherical polymer brushes?SiO₂@pCBMA?was synthesized by different RAFT polymerization process.After strictly modulating the SiO₂@pCBMA structure,like grafting density,molecular weight and degree of zwitterionation,aqueous conformation and stability of SiO₂@pCBMA have be studied.Besides,the antifouling property between SiO₂@pCBMA and various model proteins have be systematically studied by combining multiple techniques including dynamic light scattering?DLS?,turbidimetrictitration,and isothermal titration calorimetry?ITC?.In chapter four,a new functional nanoparticle,consisting of a silica core onto which short-chain zwitterions are chemically connected,was successfully prepared and showed excellent antifouling performance to protein solutions.These nanoparticles?SiO₂-ZWS?own excellent stability even in 1 M NaCl solutions for at least 48 h.The interaction between these?zwitterated?NPs and proteins were investigated systematically.The results demonstrated that the zwitterated NPs had antifouling property both in single protein solutions and serum?fetal bovine serum,FBS?.The NPs also own abundant functional groups which could conjugate with biomolecules for future applications in therapeutic and diagnostic field.In chapter five,we found a very interesting phenomenon that the end carboxyl group of short-chain zwitterion coated silica nanoparticles?SiO₂-ZWS?was difficult to be functionalized via EDC/NHS bioconjugation strategy.After that,we designed and prepared a series of bi-functionalized silica nanoparticles?SiO₂-ZWS/COOH?bycontrollingthemolarratioof3-aminopropyltriethoxysilane?APTES?andshort-chainzwitterionic organosiloxane?ZWS?to prevent nonspecific protein adsorption effectively and identify the target bio-molecules specifically.The obtained SiO₂-ZWS/COOH have the similar antifouling property compared with SiO₂-ZWS even in 50%FBS solution characterized by DLS and turbidimetric titration.It also can be functionalized with antibody for chemiluminescence enzyme immunoassay?CLEIA?with a higher detection signal than normal carboxylic silica nanoparticles?SiO₂-COOH?.These bi-functionalized silica nanoparticles have a great potential application in diagnostic and therapeutic field.