Synthesis And Investigation Of Photocontrollable Polymeric Hydrogen Sulfide

Hydrogen sulfide(H2S) is a newly recognized signaling molecule with very potent cytoprotective actions. Although the fields of H2 S physiology and pharmacology have been rapidly growing in recent years, a number of fundamental issues still need to be addressed to advance our understanding of the biology and clinical potential of H2 S in the future. To fully harness the biological activities and to further develop its applications in biology and medicine, the development of new resources of H2 S donors is critical and has become a rapidly growing field over the last few years. Herein, we rationally designed and synthesized a new ideal H2 S donor using the concept of polymeric drug delivery and stimuli-responsiveness. This thesis consists of three parts:Part 1. A highly water soluble polymeric H2 S donor poly(AEMATK10-co-EGMA60) was synthesized by RAFT polymerization and following functionalization of pendant ketone groups with 2-Nitrobenzenemethanethiol. The polymer released H2 S when triggered by irradiation of UV light and the release kinetic was dependent on the irradiation power. The cell viability data show that the polymeric donor was noncytotoxic and biocompatible. The cellular uptake data show that the polymeric H2 S donor can be uptaken up by cells with photocontrollable intracellular H2 S release.Part 2. The mPEG-OOCCH2CH2COCH3 was synthesized through an esterification reaction between mPEG-OH and levulinic acid using HfCl4·THF as catalyst. Then mPEG-OOCCH2CH2COCH3 was coupled with 2-Nitrobenzeneme-thanethiol to obtain mPEG-TK. Finally, liposome based photocontrollable hydrogen sulfide donor was fabricated after self-assemble of mPEG-TK in aqueous solution. The critical micellar concentration of mPEG-TK, the time-dependent release of H2 S and Encapsulation of Nile Red were also conducted.Part 3. The homopolymer Poly(AEMA)50 was synthesized by RAFT polymerization of monomer AEMA first andthen Poly(AEMA)50 was further polymerized with monomer OEGMA to synthesize of block copolymer Poly(AEMA50-b-OEGMA75) Finally, the block copolymer Poly(AEMA50-b-OEGMA75) was coupled with 2-Nitrobenzenemethanethiol to obtain block copolymer Poly(TK50-b-OEGMA75) as the UV-sens itive hydrogen sulfide donor. In order to overcome the limitation of UV lightin biology, upconverting nanoparticles(UCNPs) of β-NaYF4:Tm3+0.5 mol%, Yb3+ 30mol%/β-Na YF4 was encapsulated inside the micelles, which is self-assembled by block copolymer Poly(TK50-b-OEGMA75). The H2 S release property was conducted after irradiation of the micellar solution under 980 nm near infrared light.