Preparation And Photodynamic Activity Of Nanometer Modified C13~1-dicyanogen Substituted Chlorophyll Photosensitizer

Photodynamic therapy（PDT）is an increasingly recognized alternative to traditional cancer therapies.There are three main elements of PDT treatment,namely light,photosensitizer and oxygen.However,the hydrophobicity and poor targeting selectivity of most second-generation photosensitizers（PS）limit the efficacy of PDT.Experiment was designed and synthesized a new type of photosensitizer,with focal magnesium chlorophyllin off-a methyl ester（MPPa）as raw material,based on its structure are introduced in hydroxy,17 ester hydrolysis of carboxyl,improve the water soluble of photosensitizer,continue to 2 cyano,introduced in 13¹,increase the conjugate structure,make the ultraviolet absorption increased to 712.5 nm,create tumor penetration depth deeper photosensitizer 3-[1-hydroxyethyl]-3-devinyl-13¹-β,β-dicyanomethylene-13¹-deoxopyropheophorbide-a（HNPa）.Magnetic chitosan/GO nanomaterials were designed and prepared,and the composite photosensitizer MCGO-HNPa was successfully loaded with the photosensitizer HNPa.The composite material（MCGO-HNPa）has high stability,good water solubility,biocompatibility,expected magnetic targeting and good optical stability.Studies have shown that MCGO nanomaterials can promote the production and release of monomorphic oxygen.In vitro cell uptake experiments have shown that MCGO nanomaterials have the ability to accelerate the entry of HNPa drugs into tumor nuclei,and the drug release behavior is pH sensitive.MTT detection of human hepatocellular carcinoma cell line HepG-2 clearly showed that the MCGO-HNPa composite had a low dark toxicity and could effectively lead to cell damage and apoptosis under light.At the same time,studies on the photodynamic mechanism have shown that type I and type II photodynamic reactions can occur simultaneously in the PDT process,and their relative contributions depend on the type and dose of photosensitizer.Since ¹O₂ mediated tumor therapy is highly dependent on an adequate and continuous supply of O₂,the efficiency of PDT is disturbed under hypoxia.Fe₃O₄@Si O₂mesoporous materials were prepared,and the compound drug Fe3O4@Si O2-ART-HNPa was successfully loaded with artemisinin（ART）and photosensitizer（HNPa）.ART can produce ROS with Fe²⁺through pH-mediated fenton reaction process.Studies have shown that in the tumor microenvironment,Fe3O4@Si O2 nano-carrier can easily release Fe²⁺through weak acid etching.After PDT,the reaction between ART and Fe²⁺can continue to play a therapeutic role in the tumor hypoxia environment.In addition,it was found that NIR irradiation can partially increase the production of reactive oxygen species to enhance anti-tumor therapy.All the results showed that the Fe₃O₄@Si O₂-ART-HNPa nanocomplex could well overcome the existing obstacles of hypoxia in the tumor microenvironment in PDT and had a good application prospect.In order to overcome the serious adverse reactions,multidrug resistance（MDR）in cancer treatment and traditional chemotherapy drugs to tumor tissue nonspecific and single PDT due to the low efficiency within the tumor hypoxia environment,experimental folic acid was prepared by coupling the chitosan coated adriamycin DOX and photosensitizer HNPa nanoparticles and disulfide bond connected with graphene oxide compounds GFCDH,which has the function of fluorescence imaging GFCDH nanomaterials as endogenous tumor microenvironment stimulation to activate a switch control drug treatment"from a to complete"multimodal integration of nano platform to enhance cell response to drug delivery,realize the FA tumor targeting coordinated chemical and sunlight,photodynamic therapy has a broad application prospect in strengthening anti-cancer treatment.A series of characterization was carried out on the synthesis of the new nano-complex,including transmission electron microscopy,zeta potential test,DLS measurement,UV,IR,Raman spectroscopy,fluorescence emission spectrum,magnetic saturation curve measurement,XRD,etc.At the same time,in vitro drug release experiment,singlet oxygen production rate determination,photobleaching experiment,cell phagocytosis,cytotoxicity experiment,cell morphology observation and reaction mechanism experiment were carried out.All the experimental results show that the new nanocomposite has a good prospect in the treatment of cancer.