Detection Imaging And Light-controlled Release Of Signaling Molecules Hydrogen Polysulfide And Nitric Oxide

Hydrogen polysulfide,a member of reactive sulfur species,is primarily generated during the crosstalk between H₂S and reactive oxygen species（ROS）,which plays important role in physiological and pathological processes.Ferroptosis is a new non-classical mode of cell death,in which ROS-associated lipid peroxidation and iron-dependent accumulation are the main features.However,the biological effects of H₂S_non ferroptosis and the detailed mechanisms of action remain poorly understood.Thus,there is an urgent need to develop highly selective and sensitive chemical tools for monitoring H₂S_n in living cells.Nitric oxide（NO）,as a common gas signal molecule in cells,is closely related to the occurrence,development and apoptosis of tumors.In recent years,the use of NO in tumor therapy has become a research hotspot for researchers,but its application has been greatly restricted due to its easy diffusion and short half-life.Therefore,the development of a nitric oxide donor that can achieve controlled release of NO,has good biocompatibility and excellent stability is of great significance for the treatment of tumors.In the second chapter,we developed a two-photon fluorescent probe（PSP）based on 6-vinylnaphthalen-2-ol and nitro-activated fluorobenzoate for specifically imaging H₂S_n in live cells and tumor spheroids.This probe exhibited a sensitive and selective response to H₂S_n,which had been used for imaging exogenous and endogenous H₂S_n in living cells by confocal imaging and high content imaging.PSP exhibits excellent photo-stability and two-photon imaging performance when irradiating at 880 nm in 3D He La multicellular tumor spheroids.Importantly,our studies revealed that H₂S_n levels were significantly up-regulated during ferroptosis.These excellent properties ensure that PSP is a promising two-photon probe for exploring the biological and pathological effects of H₂S_n during ferroptosis.In the third chapter,we developed a light-controlled NO donor small molecule prodrug（AMNO）based on the naphthalimide structure.AMNO can be quickly and effectively activated under the synergistic effect of light(λ_ex=405 nm,5 s)and glutathione（GSH）,releasing signal molecule NO and turning on the fluorescent signal;it will not be activated without light.Confocal imaging technology further confirmed that AMNO can also be activated in tumor cells,and the degree of activation is affected by the content of GSH,which is consistent with the GSH-dependent activation mode in vitro.Therefore,it can realize the controllable targeted release of NO in tumor cells and cell imaging.Importantly,our research found that AMNO exhibits excellent anti-tumor activity under light conditions and can overcome cisplatin resistance of tumor cells,providing the possibility for targeted treatment of cancer.In short,comprehensively considering the current research status of gas signal molecules hydrogen polysulfide（H₂S_n）and nitric oxide（NO）in the physiological and pathological processes,adopting fluorescent molecular probes and prodrug design strategies,the H₂S_n two-photon fluorescent molecular probe PSP and light-controlled release NO donor small molecule prodrug AMNO were constructed based on the dipolarized naphthalene platform.It is hoped that this research work will provide new ideas for subsequent cancer diagnosis and treatment.