Design Of Tumor And Nephritis Diagnosis And Treatment System Based On ROS/CO

Photodynamic therapy(PDT)is a tumor treatment method that has been used clinically.Its principle is to use a light source to excite a photosensitizer to release reactive oxygen species(ROS)that can damage tumor cells.Compared with traditional therapies,PDT has the advantages of less side effects and strong selectivity;however,due to insufficient oxygen concentration in the tumor microenvironment and insufficient tumor targeting of photosensitizers,the therapeutic effect of PDT is not satisfactory.A photosensitizer with tumor targeting function and low oxygen consumption during PDT is an effective strategy to solve the above problems.Inflammation plays an essential role in cancer evolution,and detecting it early could kill cancer in the first place.Nephritis is a common disease,but the current detection methods are still not sensitive enough.They cannot reflect the rapid changes in renal function,which will lead to the deterioration of the patient's condition and increase the difficulty of treatment.Therefore,the accuracy of early diagnosis of nephritis needs to be improved.This paper focuses on the above two issues,and its leading research contents and results are as follows:1.Research on the synthesis of carbonyl iron-sulfur phthalocyanine based on Type?mechanism and its PDT anti-tumor activityDue to dysplasia of tumor tissue,the oxygen concentration in the tumor microenvironment is low,and the PDT process consumes oxygen,which reduces the efficiency of ROS generation,which will lead to the decrease of PDT activity.The photosensitizers used clinically are mainly active based on the Type II mechanism,which is highly dependent on oxygen concentration.In this chapter,tetra-substituted formyl mercaptoethylamine zinc phthalocyanine(Zn Pc-SH)was synthesized and coordinated with triiron dodecacarbonyl(Fe CO)to form nanoparticles(Zn Pc-Fe CO).The nanoparticles are magnetic and can realize the tumor tissue targeting function driven by the magnetic field.It generates a large amount of ROS through the Type I mechanism,which reduces the dependence of PDT on oxygen.In addition,ROS promotes the release of CO from the composite nanoparticles,which can expand the blood vessels at the tumor site and promote the enrichment of nanomedicine at the tumor site.Both in vivo and in vitro experiments show that Zn Pc-Fe CO has good anti-tumor activity.2.Research on a new method of efficient diagnosis and treatment of nephritisNephritis is a common kidney disease that is mediated by immune mechanisms and involves inflammatory mediators.The current clinical diagnosis methods are not sensitive enough to reflect changes in renal function in time.As an alternative detection method,the optical probe-based fluorescence detection method has the advantages of high sensitivity,non-invasive,rapid,and in-situ detection.After nephritis occurs,the concentration of H₂O₂ will be significantly increased to more than 50?M,which is much higher than that of normal kidney cells.In this chapter,a highly sensitive near-infrared H₂O₂ probe(NPS-H₂O₂)was synthesized,and the kidney targeting carrier Ser-PAMAM(G3)with different chirality was prepared and screened.The probe NPS-H₂O₂ and the anti-inflammatory drug pentacarbonyl Manganese bromide(CORM)is loaded in Ser-PAMAM to form CORM@NPS-H₂O₂@Ser-PAMAM nanoparticles.After successfully establishing a mouse nephritis model,the nanoparticles are easily enriched in the kidneys because their size is less than 10 nm after injecting into the mice through the tail vein.The H₂O₂ in the nephritis site transforms the structure of the probe NPS-H₂O₂ into NPS.After being excited by the 647 nm light source,it emits near-infrared fluorescence to realize the in-situ diagnosis of nephritis.H₂O₂ catalyzes CORM decomposition to generate CO to relieve inflammation and finally realize the integration of diagnosis and treatment of nephritis.