Synthesis Of Functional Polymers From Living Radical Polymerizations And Applications In Drug Delivery,Dye Sensitization And Bio-imaging

Functional polymers contributed greatly to the daily life.With the development of controlled radial polymerizations(CRP),various functional polymers/copolymers could be synthesized with controlled molecular weights and low polydispersities,which encourage the applications in different areas.This addressed the disadvantages of polymers prepared from conventional radical polymerizations.In this thesis,we synthesized several functional polymers/copolymers via CRP,and explored the applications in preparation of organic nanomedicine(drug delivery),dye-sensitized materials,and surface modification of inorganic nanoparticles.Enzyme-triggered cleavable polymer nanoparticles with active targeting ability were also synthesized,which had the potential application in bio-imaging such as MRI and SPECT.The main works are summarized as follows:(1)The branched block micro-crosslinking copolymer poly(polyethylene glycol methyl ether-block-(n-butyl methacrylate-copoly-ethylene glycol dimethacrylate))ie.P(OEGMA-b-(nBMA-co-EGDMA)was synthesized by atom transfer radical polymerization(ATRP).Subsequently,the hydrophobic drugs/dyes were prepared by solvent evaporation using the micro-crosslinking copolymer.The hydrophobic drug nanoparticles loaded into the nano-polymer were successfully prepared.According to the properties of the upper critical dissolution temperature of hydrophobic block p(nBMA)in methanol,microcrosslinked copolymers with different degree of polymerization were prepared by changing the degree of polymerization of pBMA in the polymerization system.The electron microscopic and dynamic light scattering particle size diagrams of nanoparticles loaded with drugs were measured.The results show that block copolymers with different target compounds can be synthesized and optimized by reasonably designing and choosing block monomers and block chain lengths.Solvent evaporation combined with slightly crosslinked branched block copolymers is a very effective method for preparing water-borne drug nanoparticles.(2)Linear block polymer polyacrylic acid-poly(polyethylene glycol methyl ether)ie.PAA-POEGMA was synthesized by reversible addition-fragmentation chain transfer polymerization(RAFT).By adjusting the ratio of each block,diblock copolymers with different Mw were obtained,which were used in surface modification of inorganic particles.Aqueous suspension of mono-dispersed and aggregates of NaGdF4 nanoparticles have been prepared.Morphology and size of the obtained particles have been characterized by transmission electron microscopy(TEM)and dynamic light scattering(DLS).Meanwhile,the linear block polymer was also used to stabilize the cubic Fe3O4 nanoparticles in water.The uniform stable aqueous suspension of Fe3O4 nanoparticles were also obtained.The obtained water-dispersible nano-materials have potential applications in bioimaging.(3)Hydrophilic polymer dye poly(poly(ethylene glycol)methacrylate-dye)ie.POEGMA-OH-IR was synthesized by reversible addition-fragmentation chain transfer polymerization(RAFT),which could sensitize the element Nd.The emission peak width of the unmodified NTd was very narrow and emission intensity was low.After the modification,we found that the peak intensity increased drastically.Peak shift was also observed:when small amount of dyes is added,the sensitization effect of Nd shift from 808 nm to 1060 nm.When further increasing the the amount of dyes,the blue shift phenomenon of polymer was obvious.This work could be applied in bio-imaging and solar energy research.(4)Enzyme-triggered cleavable polymer nanoparticles(CPN)conjugated with AIE segments has been by reversible addition-fragmentation chain transfer polymerization(RAFT)in two steps.The hydrophobic nanoparticles core consisted of AIE and cleavable peptide bridge segment(enzyme MMPs triggered-cleavage),while hydrophilic PEG built the shell.The corona of the nanoparticles was conjugated with peptide ACPP,which could active-targeting tumor cell.On approaching tumor cell,the nanoparticles would decompose due to the cleavage of the small peptide bridge,resulted in the formation of linear block copolymers which could penetrated into the cell.Original MRI measurement suggested that the r1 is 9.75 mM-1 S-1 which was almost 2.5 times of the commercial contrast agent Gd-DTPA.TEM and DLS results indicated the complete decompose of the nanoparticles after addition of MMP 2 or 9 in-vitro.Cell experiments also suggested that the linear polymers obtained after the cleavage of nanoparticles could penetrate into the tumor cell effectively.The nanoparticles could find applications in bio-imaging and targeting drug delivery.