Light-controlled H₂S Production In Coacervate Protocell And Regulation Of Cell Proliferation

As a new type of gas signal molecule,hydrogen sulfide(H₂S)participates in many physiological and pathological processes.It has potential applications in anti-inflammatory,anti-oxidant,neurodegenerative diseases and cancer treatment.The physiological effects of H₂S are concentration-dependent and time-dependent.How to achieve the controlled production and release of H₂S is an important challenge for the physiological application of H₂S.Light-induced H₂S release has gained considerable significance because of the ability to provide spatiotemporal control over H₂S release,and the location,the time and intensity of irradiated light can control the amount and duration of H₂S release,and it is easy to operate.As a good carrier,coacervate microdroplets have some unique properties,such as selective molecular enrichment,liquid fluidity and dynamic assembly.This thesis combines the precise strategy of light-controlled nanomedicine and the high-efficient loading capacity of coacervate microdroplet protocells,providing a new idea for the controllable generation and physiological application of H₂S.In this paper,coacervate microdroplets were used as carriers,combined with thermally unstable H₂S donors and photothermal nanoparticles to construct functionalized coacervate protocells that can respond to near-infrared photothermal,providing a simple and practical method for remote control of real cell behavior.This research work includes the following two aspects:1.Construction of coacervate protocells-containing photothermal nanocomposites for photo-controlled release of H₂S.A H₂S generation and release system with a controllable response to near-infrared light(NIR)was constructed by using a photothermal nanocomposite composed of glycine dithiocarbate(Gly-DTC)and gold-silver alloy-coated gold plasma nanoparticles(Au@Ag-Au p NPs),which were loaded in coacervate microdroplet protocells.Ultraviolet spectroscopy was used to characterize the loading amount of the photothermal nanocomposites in the coacervate protocells as 0.7 mg/mg.Under irradiation of NIR,photothermal nanoparticles Au@Ag-Au p NPs converted light energy into heat energy,and the elevated temperature promoted the effective release of H₂S from the thermally liable H₂S donor Gly-DTC.The amount of H₂S released from coacervate protocells loaded with nanocomposites(4.8 mg/m L)reached up to 320?M after 780 nm NIR light irradiation for 10 min.In this work,functionalized coacervate protocells triggered by NIR light to release H₂S gas photothermally has been constructed,which can control and efficiently produce H₂S in real time and diffuse slowly to the external.It is expected to serve as a new form of gas production and provide a new idea for the biomedical application of H₂S gas.2.Light-controlled production of H₂S by functionalized coacervate protocells for the regulation of growth behavior in real cells.On the basis of the first work,the functionalized coacervate protocells and the real cells were fixed in the left and right chambers of the microfluidic channel respectively,and the information exchange between the coacervate protocells and the real cells was established by using the photocontrolled H₂S production of the functionalized coacervate protocells.The controlled H₂S production was regulated by the light time and power of the functionalized coacervate protocells,which realized the antioxidant regulation and proliferation of oxidatively damaged cells.When 780 nm NIR light irradiated the coacervate protocells colony for 10 min,the generated H₂S diffused to the real cell communities,and had obvious anti-oxidative damage effect on the cell communities damaged by H₂O₂.The activity of lactate dehydrogenase(LDH)was reduced from 62.8%to 35.5%,LDH leakage was inhibited,and cell viability was restored from 48.4%to 88.9%.In this work,the production of H₂S through light,plays a regulatory role in cell anti-oxidation and cell proliferation,and is expected to be used in cell physiological regulation and biomedical applications.