Research And Application Of Photo-responsive Polymer Materials For Releasing Carbon Monoxide

Nitric oxide(NO),carbon monoxide(CO)and hydrogen sulfide(H2S)are endogenous gases with biological effects and membrane permeability,which have been shown to play an important role in neuronal excitability and homeostasis.CO is an endogenous molecule produced by heme oxygenase in the degradation of heme.Physiological concentration of CO can mediate the signal transduction of the brain,liver,and endothelium;morever,CO is also involved in the regulation of vascular tone and the production of inflammatory mediators,and is related to the mechanisms of ischemic injury,cell proliferation,and bacterial infections.To avoid the lack of specificity and toxicity at high concentrations when inhaling CO gas,Motterlini and colleagues introduced CO-releasing molecule(CORM).Most of CORMs release CO by thermal activation or hydrolysis in biological buffers,and can also be activated by internal triggers(such as enzymatic reactions)or external triggers(such as light)to achieve controlled release.However,traditional low-molecular-weight CORMs diffuse rapidly after administration and release CO before reaching the biological target,which cannot meet the minimum valid concentration(MVC)in the target tissue.To solve this problem,nanomaterials such as polymers have been used as carriers to release CO.The behavior of stimulus-responsive polymers can be adjusted by regulating the internal or external environment,physical and chemical properties of these polymers can change drastically when exposed to stimuli such as temperature,pH,redox,ionic strength,and light.Light has received widespread attention because of its characteristics of spatial-temporal controllable and no need for additional reagents.In addition,the radiation parameters such as intensity and wavelength of the light,and radiation time can be easily manipulated to adapt to the requirements of different systems.Due to the advantages of adjustable particle size and better tissue penetration ability,photo-responsive nanocarriers can improve the pharmacokinetics and biodistribution of chemotherapeutics,and have become an effective tool for targeted therapy.So far,physical loading,covalent modification and direct polymerization methods have been used to integrate CORMs into polymer materials,which can not only improve stability,extend CO release time,target pathological tissues effectively,but also have excellent therapeutic potential for related diseases.Based on this,this thesis is committed to preparing a photo-responsive CO polymer material with good stability and self-reporting release,and studying its ability to release CO in response to light and potential anti-inflammatory biological applications.The specific content is divided into the following two parts:1.Synthesize and prepare monomers of 3-hydroxyflavone(3-HF)derivatives containing dihydroxyl groups,study the response behavior and CO release of monomers,and use high-resolution mass spectrometer to analyze the ion fragments generated by irradiation to explore the photoresponse mechanism of monomers;Subsequently,the monomer were separately polycondensed with isophorone diisocyanate(IPDI)and polyethylene glycol(PEG),and the photosensitive 3-HF moiety was introduced into the polymer backbone to construct a photo-mediated degradable polymer for CO release.Then the polymer was fully characterized and its photoresponse behavior was comprehensively studied.2.The CO-releasing triblock polymer(CORTC)has complete end-capping,and is composed of hydrophilic ends with a hydrophobic CO-releasing middle block.The micellar nanoparticles with good stability are prepared by self-assembly methods.Under visible light irradiation,the polymer chain scission occurs,and the micellar nanoparticles can release CO in response.Biological experimental studies have shown that the micellar system has good biocompatibility and can alleviate the level of nitrite in macrophages induced by lipopolysaccharide(LPS),exhibiting excellent anti-inflammatory effects.