Biointerfacing Polymeric Multilayer Capsules For Anticancer Therapy

Phospholipid bilayer,as the most important and best known self-assembled structure in nature,can modify on the surface of the synthetic materials to significantly improve their biocompatibility.Due to the mild preparation conditions,diverse loading method,and easy to surface functionalization,layer-by-layer self-assembled polymer capsules have broad application prospects in the area of medical science,biochemistry,materials science and so on.Up to now,polymer capsules are mainly focused on the in vitro antitumor therapy,while in vivo anticancer therapy is relatively rare.Based on this,in this thesis we prepared,characterized,functionalized of biointerfacing layer-by-layer self-assembled polymeric capsules for in vivo anticancer therapy.We fabricated the polyelectrolyte multilayers supported lipid bilayers by combing the layer-by-layer self-assembly technique and the vesicle fusion method.Several experimental techniques such as quartz crystal microbalance,fluorescence recovery after photobleaching,confocal laser scanning microscope,and multi-scale molecular simulation were employed to study the adsorption and rupture of vesicles on the polyelectrolyte multilayers under different conditions,as well as the forming process of planar or spherical polyelectrolyte multilayer-cushioned lipid bilayers.Our results showed that lipid bilayers could be conformed on the surface of polyelectrolyte multilayers which is composed of chitosan and alginate at pH 6.5.The diffusion coefficient of lipid bilayers was measured to be 1.87 μm2/s,while reaching 1.10 μm2/s when the substrate changed to the three-dimensional spherical multilayers.Controlled assembly of polyelectrolyte multilayer-cushioned lipid bilayers can be achieved by optimal forming conditions,providing a reference for the design and preparation of biomembrane based antitumor platform.Chitosan and alginate were selected as wall materials to prepare polyelectrolyte microcapsules by layer-by-layer self-assembly.In order to obtain enhanced photothermal effect,gold nanorods were also assembled into the walls of microcapsules.An effective adjustment of the mechanical properties of the microcapsules can be achieved by assembling the layers and the density of gold nanorods.Lipid bilayers consisted of folic acid modified phospholipid can be assembled on the surface of microcapsules.The results demonstrate that the biointerfacing microcapsules can exhibit similar deformability like tha t of red blood cells in the blood environment and accumulated behaviors at the tumor site.When the tumor site was exposed to near-infrared laser with high laser intensity,the photothermal effect of gold nanorods in the wall of microcapsules was activated,followed by the generation of vapor bubbles.The volume of vapor bubbles can be modulated by the incident laser intensity of near-infrared laser.The rapid expansion of the bubble volume teared and destroyed the tumor cells,resulting in effective in vivo antitumor therapy.Exploiting the hollow structure of microcapsules and encapsulated ability of biomembrane,we built up a novel drug carriers based on gold nanorods and chitosan-alginate microcapsules.Hydrophilic anticancer drug doxorubicin was loaded into the microcapsules and encapsulated by lipid bilayers.After irradiated with a low power near-infrared laser,the gold nanorods of microcapsules converted the adsorbed light energy to heat,which destroy the structural integrity of the lipid bilayers and the walls of microcapsules,and result in the controlled drug release.The results show that lipid bilayers significantly reduce the permeability of the microcapsules,and thus effectivly encapsulate the water-soluble small molecule drugs.Near-infrared laser mediated drug controlled release can effectively inhibit tumor growth and prevent metastases in vivo without obvious side effects.By varying the size of the templates,we can change the size of polymeric capsules from micrometer to nanometer.In order to obtain magnetically enhanced targeting anticancer system,chitosan,alginate,Fe3O4 magnetic nanoparticles were selected to prepare the polymeric nanocapsules.Hypocrellin as photosensitizer was loaded into the hollow structure of nanocapsules for photodynamic therapy.The surface of nanocapsules was decorated with red blood cell membrane to protect nanocapsules from clearance by immune system,thus improving the transport efficiency and therapeutic effect of the drug carriers.Under laser irr adiation,photosensitizer in the nanocapsules was activated to produce reactive singlet oxygen to achieve in vivo photodynamic antitumor purposes.Based on the bionic design and controlled layer-by-layer self-assembly of polymeric capsules,we successfully prepared a series of biointerfacing polymeric capsules for in vivo anticancer therapy through photothermal therapy,chemotherapy,and photodynamic therapy.Due to their excellent biocompatibilty,biointerfacing polymeric capsules have a bright prospect in the application in the biomedical field,and have the potential to be applied in clinical settings.