Synthesis,Self-assembly And Applications Of UV-and Reduction-responsive Amphiphilic Block Copolymers

Stimulus-responsive polymeric carriers as an efficient vehicle for transporting drugs have some advantages of improving solubility and stability of insoluble drugs and reducing side effects of non-pathological sites by enhanced permeability and retention effect(EPR effect).Moreover,in the pathological sites,especially in tumor tissues(low pH,high osmotic pressure,reductive microenvironment,etc.)under the conditions of external stimulus,the microstructures or hydrophilic-hydrophobic balance of amphiphilic block copolymers have been significantly changed,so as to be able to control the release of drugs in the pathological sites.Therefore,stimulus-responsive polymeric drug carriers have become an important research content in the fields of biomedicine.In this paper,we have mainly studied self-assembly of responsive block copolymers to form nano-drug carriers containing different morphologies,and then under conditions of external stimulus,the microstructures or hydrophilic-hydrophobic balance of amphiphilic block copolymer or hydrophobic-hydrophobic were changed,utulized to control the release of drugs.The detail descriptions are as follows.1.PEG-b-P(STPMA-co-CPTM)and PEG-b-PSTPMA-b-PCPTM,two kinds of amphiphilic block copolymers,prepared by reversible addition-fragmentation chain transfer polymerization(RAFT Polymerization),which are sequentially responsive to UV light and reductive environment,self-assembled to form vesicle or compound vesicle nano-drug carriers by slowly adding the deionized water into co-solvent of block copolymers containing spirothiopyran and disulfide-linked camptothecin prodrug.Thiophenol produced by ultraviolet irradiation,is exchanged with disulfide bond,and this artificial constituted reductive microenvironment makes camptothecin drug released.2.Reductive microenvironment,produced by ring opening of spirothiopyran by ultraviolet irradiation,where thiophenol may be exchanged with disulfide bond,couldn't make camptothecin drug released efficiently in chapter 1.As a consequence,resulting thiol reactive activity must be higher in order to exchange with disulfide bond efficiently,and then ring-forming release of camptothecin.Therefore,production methods of mercapto group were replaced by o-nitrobenzyl sulfanyl group.The PEG-b-P(NTMA-co-CPTM)amphiphilic block copolymers,prepared by RAFT polymerization,was used to form a compound vesicle nano-drug carriers by adding slowly deionized water into co-solvent,with side chains containing o-nitrobenzyl sulfanyl and disulfide-linked camptothecin prodrug of hydrophobic block segment.And thiol groups were generated by ultraviolet irradiation,exchanged with disulfide bond and released camptothecin,which artificially constituted microenvironment played a role in inhibiting or killing tumor cells.3.ACL(Aldehyde Capture Ligation)chemical reaction can make salicylaldehyde ester and amine compounds react to form hemiaminal intermediates.Because of more closer distance of amino and ester bond,generating amide bond was rapid occurrence by acyl transfer,with drop of salicylaldehyde as the same time.The hydrophobic block segments of amphiphilic block copolymers PEG-b-PFPXE designed in this section and contained salicylaldehyde esters,self-assembled to form vesicles.PEG-b-PFPXE vesicles were in more high concentrations of glutathione(GSH)in tumor cells than normal cells,which resulted in the change of the microstructures of block coplymers and affected amphiphipathic features so that hydrophilic-hydrophobic balance was destroyed.Eventually,morphology of vesicles has been changed,along with release of hydrophilic drugs.