Synthesis And Characterization Of Amphiphilic Polyamino Acid Materials Containing Thioether Groups

Reactive oxygen species（ROS）in biological tissues are in a state of dynamic balance.However,many diseases,such as cancer and inflammation,are accompanied by a long-term increase in ROS.There are over-expressed reactive oxygen species in inflammatory tissues,and the high level of reactive oxygen species in inflammatory sites not only damages tissues but also delays wound healing.These conditions have inspired researchers to use pathological areas with high levels of reactive oxygen species as targets to release drugs.Polyamino acid materials have good biodegradability,biocompatibility and regular secondary structure,and are widely used in biomedical field.Here,we synthesized an anti-cancer drug delivery carrier with oxidation responsiveness by using amino-terminal polyethylene glycol as a macro initiator to initiate the ring-opening polymerization of N-carboxyanhydrides bearing thioether pedants.When the chain length of hydrophilic polyethylene glycol and polymerization degree of polyaminoacids decreased,a temperature-sensitive hydrogel could be obtained.（1）Thioether was introduced into glutamic acid,and N-carboxyanhydrides bearing thioether pedants was initiated by polyethylene glycol with amino group with molecular weight of 5000 to obtain block copolymer m PEG_5k-b-PMLG,which was self-assembled into spherical nanoparticles（NPs）with diameter of about 68.3 nm in water.The measurement of ¹H NMR shows that the hydrophobic thioether suspension in nanoparticles can be selectively oxidized to hydrophilic sulfoxide groups by hydrogen peroxide,which will lead to the dissociation of NPs.The in vitro drug release profiles showed that the encapsulated Nile red was selectively released under the trigger of 10 m M hydrogen peroxide in PBS.Finally,the anticancer drug doxorubicin（Dox）was encapsulated in NPs,and the obtained NPs/Dox showed an improved antitumor effect in 4T1 tumor-bearing mice,and its cardiotoxicity was lower than that of free Dox.These results indicate that m PEG_5k-b-PMLG NPs are promissing for anticancer drug delivery.（2）A block copolymer,m PEG_2k-b-PMLG,was obtained by using PEG with amino group with molecular weight of 2000 as initiator and reducing the degree of polymerization,and hydrogel could be formed at 35℃.The ¹H NMR show that the thioether group can be oxidized into a sulfoxide group by 10 m M H₂O₂,and rheological tests indicate that the material is temperature sensitive.SEM observed a substantial microporous structure and sufficient space inside the hydrogel,with a rationale for drug loading.In vitro cell experiments showed that the survival rate of L929 mice under hydrogel protection at 0.25and 0.125 m M H₂O₂ exceeded 90%,successfully reduced cell damage in high ROS environment,and MTT results showed that the products after hydrogel oxidation were not cytotoxic.These results indicate that m PEG_2k-b-PMLG is expected to be used in anti-inflammatory field.