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Copper-iron-based Nano-photothermal Agents And Drug Delivery Systems In The Treatment Of Colon Cancer

Posted on:2022-10-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y C DuFull Text:PDF
GTID:1484306329972529Subject:Surgery
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Colorectal cancer is a common malignant tumor of the digestive tract,and its morbidity and mortality are among the top malignant tumors in the world.At present,the main treatment for colorectal cancer is multidisciplinary comprehensive treatment based on surgical treatment.However,the survival of patients is still affected by postoperative recurrence and metastasis.Therefore,it is necessary to cooperate with perioperative adjuvant treatment to reduce the risk of recurrence and metastasis.risk.However,both chemotherapy and radiotherapy have their limitations,leading to unsatisfactory therapeutic effects and many adverse reactions.Therefore,there is an urgent need for new effective adjuvant treatment methods with few side effects.With the development of science and technology in recent years,nanotechnology and nanomedicine are developing rapidly.According to the characteristics of acidic pH value of microenvironment and the EPR effect of tumor tissue that the capillary endothelial cells in the tumor tissue have large gaps,incomplete structures,and lack of lymphatic drainage,which makes it easier for nanoparticles of a specific size(10-400 nm)to penetrate into the tumor tissue and are not easy to be discharged,resulting in retention and accumulation.Nanotechnology assisted therapy such as photothermotherapy and drug delivery system appears.Photothermal therapy can convert light energy into heat energy and melt tumor by using non-toxic near infrared light irradiation with nano materials with photothermal conversion performance.It has some advantages of selectivity,controllable operation and low invasiveness.Because of its deep tissue penetration depth,large absorption coefficient and small harm to human body,the near infrared light with wavelength of 808 nm is widely used in the study of photothermal treatment.Drug delivery system is that nanomaterials are bound with some active molecules or drugs through chemical bonds,or by adsorption on the surface or wrapped in nano materials,and then transported to tumor tissue.Nanomaterials can be delivered to the target site effectively because of their nano size and can pass through the vascular endothelial of tumor site.Therefore,they can reduce the toxicity of drugs and improve the efficacy of drugs by reducing the free drugs in non target organs.Based on the above nanotechnology,photothermotherapy and drug delivery system have a good prospect.The following two aspects of the research are carried out in this study based on the inorganic metal copper iron nanomaterials:1.We constructed a Prussian blue-based nanomaterial PB@CuS,characterized it,understood its morphology and molecular properties,and calculated its photothermal conversion efficiency,and then performed cytotoxicity experiments,long-term toxicity experiments,and in vitro treatments of nanomaterials Experiments,in-vivo treatment experiments,NMR imaging capability tests.2.We constructed nanomaterials PDA@CFNs based on CuFe2O4,characterized them,understood their morphology,molecular properties,calculated their photothermal conversion efficiency,and used as a drug delivery system for the loading rate and release of chemotherapeutic drugs DOX,and then carry out cytotoxicity experiments,long-term toxicity experiments,in vitro treatment experiments,in vivo treatment experiments,and nuclear magnetic imaging capability tests of nanomaterials.Based on the above research,we have achieved the following results:1.PB@CuS has uniform size and good dispersion,with a diameter of about75-90 nm.The average hydrated particle size of PB@CuS is 189.9 nm.2.Under the same Fe concentration and the same power of 808 nm NIR,the heating effect of PB@CuS is stronger than that of PB;the heating effect of PB@CuS is related to the concentration of Fe and the power of NIR,and the photothermal performance is stable.3.PB@CuS-BSA has no obvious short-term and long-term toxicity.4.PB@CuS-BSA has the ability of MR imaging contrast agent in vitro and in vivo.5.PTT can effectively inhibit the growth of tumor cells and even completely ablate the tumor.The therapeutic effect of PB@CuS-BSA at the same concentration is significantly better than that of PB,with statistical differences.6.The therapeutic effect of PB@CuS-BSA+NIR on subcutaneous colon cancer in mice is better than that of PB+NIR,which is statistically different.7.The particle size of PDA@CFNs is 125 nm,with good morphology and size.8.Under the same concentration and power of 808 nm NIR,the heating effect of PDA@CFNs is stronger than that of CFNs;the heating effect of PDA@CFNs is related to the concentration of Fe and the power of NIR,and the photothermal performance is stable.9.PDA@CFNs-DOX drug delivery system has pH and NIR-responsive release performance.10.PDA@CFNs has no obvious short-term and long-term toxicity.11.PDA@CFNs has the ability of MR imaging contrast agent in vitro and in vivo.Through the analysis of the above results,we draw the following conclusions:1.PB@CuS is a photothermal agent with good photothermal performance and has no obvious long-term and short-term toxicity.Its photothermal treatment can effectively ablate the tumor tissue of subcutaneous colon cancer in mice,and has the potential to become a contrast agent for MR imaging.PB@CuS May provide a new treatment plan for colon cancer treatment.2.PDA@CFNs is a kind of photothermal agent with good photothermal performance and stable,without obvious long-term and short-term toxicity.It has the potential to become a contrast agent for MR imaging,and it can achieve the coordinated treatment of PTT and chemotherapy under the guidance of nuclear magnetism by loading DOX.PDA@CFNs May provide a new treatment plan for colon cancer treatment.
Keywords/Search Tags:Colon cancer, photothermal therapy, nano-drug delivery system, Prussian blue, tumor microenvironment
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