Self-assembly Of Responsive Branched Polymer And Homopolymer And Their Biomedical Applications

Polymer nano-vectors are widely used in drug and gene delivery because of the advantages of simple preparation and structural modification.Various responsive polymers have been designed to selectively release the loaded target molecules at lesion site.And the self-assembly of polymers is the key step for the construction of polymer nano-vectors.Most polymers used in construction of polymer nano-vectors are amphiphilic block polymers.But the self-assembly of non-amphiphilic polymers are very limited.In addition,the research about the change of intracellular physiological environment indeced by exogenous materials are limited.Actually,many chemical molecules and nanomaterials not only can induce generation of some new molecules but also deplete some existing molecules in the cell after they enter in cells,thereby substantially changing intracellular physiological environment,which in return may have unexpected effects on the activity of protein and gene.In this dissertation,we focus on the self-assembly of non-amphiphilic branched polymers in nanodroplets and the self-assembly of non-amphiphilic homopolymers in the presence of multiple noncovalent interactions,as well as the construction of responsive nanomicelles and their applications in gene delivery.Specifically,the dissertation can be further categorized into the following three parts1.A temperature-responsive PEG-based branched polymer with disulfide bonds in its backbone is prepared via RAFT polymerization.This PEG-based branched polymer is not amphiphlic,but it can self-assemble into nanogels in water.When we restricted branched polymers within nanodroplets,we observed an unexpected self-assembly behavior.In nanodroplet,the polymer can self-assemble into nanocapsules,which cannot be obtained via its assembly in solution.Furthermore,the size of nanodroplets can be easily controlled via the amount of surfactants,and thereby the size of nanocapsules can also be easily tuned.The nanocapsules are successfully used as protein/gene vectors.Besides,when a kosmotrope salt Na2HPO4 was added into the the water phase containing polymer,another unexpected assembly behavior happened,the polymer can self-assemble into vesicles.2.Based on the special self-assembly behavior of polymer in Na2HPO4 aqueous solution.We simplified the polymer structure and prepared a series of polar polymers,such as poly(propylene oxide)(PPO),poly(vinyl methylether)(PVME)and poly(N-isopropyl acrylamide)(PNIPAM).We used1H NMR and isothermal titration microcalorimetry(ITC)to characterize the binding interactions of these polymers and different ions.The results confirmed the dipole-anion interactions between these polar polymers and SCN-anion.The SCN-anion can interact with some slightly positively charged units in the homopolymers via anion-dipole interactions,which results in that there are many tiny anion-bound-regions and non-anion-bound-regions within the polymer chains.The anion-bound-regions and non-anionbound-regions can drive the homopolymers to self-assemble into multiple nanostructures in water like an amphiphilic block copolymer.3.We introduced a fluorocarbon chain into polycations,and the modified polycations can self-assembled into nanomicelles with different sizes.The micellization of polycations can drive the close packing of positively charged groups on the surfaces of the self-assembled nanomicelles,thus leading to a higher charge density of nanomicelles(+64 mV for 10 nm micelles)than polycations.Therfore,the nanomicelles exhibited high binding affinity for DNA(CE50 = 0.23)and can completely condense DNA at a low N/P ratio of 1 and achieved high gene-transfection efficacy(ca.95%in 293T cells).Besides,we constructed another responsive nanomicelles which can self-scavenge the polyplex-induced intracellular reactive oxygen species(ROS)and achieve a high gene transfection efficacy in a normal intracellular homeostasis.