Templating Assembly And Biological Behaviors Of Poly(ethylene Glycol) Particles

In order to reduce the toxic side effect of the traditional chemotherapy in cancer treatments and improve the utilization of the drug effectively,nano-drug delivery systems have attracted great attention from scientists.However,due to the complex biological environments in the body,physicochemical properties(e.g.,size,shape,stiffness,and surface chemistry)of the drug carrier significantly affect their biological behaviors.The intravenously injected drug carrier is easily recognized and cleared by the immune system,which reduces drug delivery efficacy.To prolong the circulation time of drug carriers in the body,the mostly used method is to modify the surface of the drug carriers with poly(ethylene glycol)(PEG).However,due to steric hindrance,the density of PEG modification on the surface of the carrier is not high,resulting in insufficient anti-biofouling ability of drug carriers.So how to reduce the non-specific interaction between nanocarriers and biological system and prolong the circulation time in vivo is still a great challenge.In this paper,we report the synthesis of PEG carriers with different size,shape and stiffness by templating methods and investigate the biological behaviors of PEG carriers in vitro and in vivo.This thesis includes the following three chapters.Chapter Ⅰ is focused on the introduction of the ant-biofouling concept,commonly used antifouling materials,and the preparation of drug carriers using hard and soft templating methods.The influences of the interactions between drug carriers and biological system are also summarized.In chapter Ⅱ,we report the anti-biofouling capsules composed of linear PEG(LPEG),poly(carboxybetaine methacrylate)(PCB),poly(sulfobetaine methacryloxyethyl)(PSB)and 8-arm-PEG(MPEG)capsules which are prepared by free radical polymerization using emulsion droplets as soft templates.Anticancer drug DOX can be encapsulated into capsules via electrostatic interaction.Compared with the other three types of capsules,MPEG capsules result in lowest cell interaction.MPEG capsules modified with targeting molecule of cyclic peptides containing Arg-Gly-Asp(cRGD)can specifically target U87 MG cells which overexpress αvβ3 integrin on the cell membrane surface.cRGD-modified MPEG(MPEG-RGD)capsules capsules demostrate good biocompatibility and high drug delivery efficacy.In chapter Ⅲ,sperical and red-blood-cell-like(RBC-like)mesoporous silica particles replicated from red blood cells are used as the templates for the fabrication of special and RBC-like PEG microgels,respectively.The obtained PEG microgels are well dispersed in aqueous solution and tunable degradability in the presence of reducing reagent(e.g.,glutathione).Deformation of the PEG microgels is tuned via using different concentrations of cross-linkers,where lowly cross-linked PEG microgels demonstrate better defomability in a microfluidic device.Compared with spherical PEG microgels,RBC-like PEG microgels show better deformation ability.In vivo experiments indicate that PEG microgels with different cross-linking density result in different biological behaviors.