Preparation Of Novel Amphiphilic Polymer Nanomaterials Applied In Drug Delivery

Polymer nanomaterials have been widely used because of their unique physical and chemical properties.A variety of functional polymer nanomaterials have brought new blood in biomedicine.In order to overcome the disadvantages of the poor water solubility of anticancer drugs and fluorescent imaging agents,increasing number of polymers are also used in drug delivery and surface modification of biomaterials.In this dissertation,a series of novel amphiphilic copolymer and polymer fluorescent nanoparticles have been designed and synthesized by ring opening polymerization(ROP),reversible addition-fragmentation chain transfer(RAFT)polymerization and free radical polymerization,which were then used for drug delivery and cellular imaging.Detail of our work was given as following:A set of amphiphilic poly(ethylene glycol)-b-poly(ethylene brassylate)(PEG-b-PEB)copolymers based on the PEB hydrophobic block was first synthesized by ring-opening polymerization of ethylene brassylate with an organic catalyst.The EB/PEG molar ratios and reaction time were adjusted to achieve different chain lengths of PEB.Block copolymers that were characterized by 1H NMR and GPC could self-assemble into multimorphological aggregates in aqueous solution,which were characterized by DLS and TEM.The hydrophobic doxorubicin(DOX)was chosen as a drug model and successfully encapsulated into the nanoparticles.The release kinetics of DOX were investigated too.A novel well-defined four-armed poly(ethylene brassylate)-b-poly(poly(ethylene glycol)methyl ether methacrylate)(S-PEB-b-P(PEGMA))was synthesized and self-assembled via the combination of ring-opening polymerization(ROP)and reversible addition-fragmentation chain transfer polymerization(RAFT)in this work.It proceeded firstly with the synthesis of hydrophobic four-armed star homopolymer of ethylene brassylate(EB)via ROP with organic catalyst,followed by the esterification reaction of S-PEB with chain transfer agent(CTA).Afterwards,RAFT polymerization of PEGMA monomer was initialed using PEB-based macro-RAFT agent,resulting in the target amphiphilic four-armed star copolymer.The obtained S-PEB-b-P(PEGMA)can assemble into micelles with PEB segments as core and P(PEGMA)segments as shell in aqueous solution.The self-assembly behavior was studied by dynamic light scattering(DLS)and transmission electron microscope(TEM).The micelles of S-PEB-b-P(PEGMA)exhibited higher loading capacity to the anticancer,doxorubicin(DOX).The investigation of DOX release from the micelles demonstrated that the release rate of the hydrophobic drug could be effectively controlled.Carbon dots(CDs)have aroused widespread concern due to their chemical stability,biocompatibility as well as low toxicity.Herein,polymerizable CD monomers were synthesized through amidation between hydrophobic CDs and methacryloyl chloride,emerging as a handy method of preparing different fluorescent CD monomers.The fluorescent polymerizable CDs were copolymerized with N-isopropylacrylamide(NIPAM)to form thermo-responsive fluorescent nanoparticles.The poly(NIPAM)(PNIPAM)grafted hydrophobic CDs(CDs-g-PNIPAM)have excellent dispersivity in water,rendering the hydrophobic CDs with fluorescent property in aqueous media.Moreover,CDs-g-PNIPAM nanocomposites show a remarkable thermo-responsive behavior,and the fluorescence intensity decreases progressively with the increase in temperature.Cytotoxicity tests show that CDs-g-PNIPAM nanocomposites have a great biocompatibility.When the CDs-g-PNIPAM nanocomposites were cultured with the HaCaT cells(spontaneously immortalized human skin keratinocyte)at concentration of 2000 ?g mL-1,cell viability maintained over 85%.Benefiting from copolymerization of NIPAM,the excitation-independent fluorescence of CDs-g-PNIPAM nanocomposites can be used for cellular labeling,and show long-term biostability in cellular environment.