Synethesis And Performance Of Temperature-sensitive Functionalized Polymer Materials Based On Porphyrin Derivative

Porphyrin compounds have been widely used in photodynamic therapy?PDT?due to their characteristic photo electrochemical properties.However,their poor water solubility and uneven dispersion resulted from low molecular aggregation lead to the decrease of optical properties,which limit their application in the field of biomedicine.In order to overcome the above shortcomings,and based on the characteristics of porphyrin molecules,thermo-sensitive linear and star polymers were synthesized by a series of polymerization reactions.The obtained polymers show good water solubility,thermosensitivy and biocompatibility.Moreover,they show lower lowest critical solution temperature?LCST?and good the light toxicity for L929 cells.Specific research is divided into the following parts:By RAFT polymerization methods,the porphyrin terminated poly?N-isopropylacrylamide?and poly?oligomeric ethylene glycol methyl ether methacrylate?linear block copolymer?Por-PNIPAM-b-POEGMA?were designed and synthesized.Herein,chain transfer agent?Por-DMP?was synthesized through the reaction between homemade5-?4-hydroxyphenyl?-10,15,20-threephenyl porphyrin?Por?and S-1-dodecyl-S'-??,??-dimethyl-??-aceticacid?three carbonate porphyrin esterification,porphyrin terminated poly?N-isopropylacrylamide?as a macromolecular chain transfer agent was prepared,and then reacted with monomer oligomeric ethylene glycol methyl ether methyl acrylate to obtain Por-PNIPAM-b-POEGMA.The obtained copolymer shows controllable the LCST value in 37⁴2°C by changing the copolymer chain segment content of poly?oligomericethyleneglycolmethylethermethacrylate?.The result of the MTT method shows that Por-PNIPAM-b-POEGMA has low toxicity for fibroblasts L929 in mice and human cervical cancer HeLa cell in the absence of light,but the low toxicity for the L929and high toxicity for HeLa under the red glow.Folic acid grafted poly?N-isopropyl acrylamide?and poly?methylacrylichydroxyl ethylester?linear block copolymer??Por-PNIPAM-b-PHEMA?-g-FA?were prepared by combining RAFT polymerization with esterification reaction.Herein,porphyrin-based linear block copolymer was prepared?Por-PNIPAM-b-PHEMA?by RAFT method,and then?Por-PNIPAM-b-PHEMA?-g-FA was synthesized by esterification with folic acid.The results of cell toxicity test show that the Por-PNIPAM-b-PHEMA and?Por-PNIPAM-b-PHEMA?-g-FA had low toxicity for L929 and HeLa in the absence of light;under the light,the toxicity of Por-PNIPAM-b-PHEMA and?Por-PNIPAM-b-PHEMA?-g-FA for HeLa was higher than that of the Por.The results in HeLa cells showed that?Por-PNIPAM-b-PHEMA?-g-FA was more likely to be swallowed by cells at the same time than that of Por-PNIPAM-b-PHEMA.The star block copolymer THPP-?PNIPAM-b-POEGMA?₄ of porphyrins?N-isopropyl acrylamide?and poly?oligoethylene glycol methacrylate?was synthesized by RAFT method.Herein,THPP-?PNIPAM-b-POEGMA?4 was synthesized by using 4?4-hydroxyphenyl?porphyrin?THPP?as the chain transfer agent of the core to successively react with monomer N-isopropylacrylamide and oligomermethylethermethacrylate.Controling the LCST polymers for 37-42°C,when the temperature is higher than the LCST micelle formation,compared with the linear polymer,critical micelle concentration?CMC?is lower.The results of MTT method showed that THPP-?PNIPAM-b-POEGMA?4 showed good biocompatibility and no dark toxicity for L929 cells and HeLa cells.Moreover,the toxicity of THPP-?PNIPAM-b-POEGMA?4 for HeLa cells was significantly higher than THPP,and the light toxicity for L929 cells was low.Thethermosensitiveporphyrin-basedstarblockcopolymer THPP-?PNIPAM-b-PMAGA?₄ was prepared by using the prepared THPP-?PNIPAM?₄ as the macromolecular chain transfer agent to react with homemade 2-?methyl acrylamide?glucose monomers through the RAFT polymerization method.The LCST value of THPP-?PNIPAM-b-PMAGA?₄ is 41.2°C,CMC is 0.003 mg/mL.The temperature is higher than LCST self-assembly forming micelle.The MTT results showed that the dark toxicity for L929 and HeLa cells was low,and the phototoxicity for HeLa cells was higher than that of L929 cells.The results showed that THPP-?PNIPAM-b-PMAGA?4 had increased the uptake of HeLa cells over time.