Developing Novel Iodine Based Hydrogel For Biological Activity And Photothermal Therapy Of Cancer

Cancer is one of the major diseases which threaten human health.With the advancement and development of science and technology,traditional clinical treatment methods such as surgery,chemotherapy and radiotherapy have greatly prolonged the survival rate of patients.However,due to the defects of traditional clinical treatment methods,incomplete treatment and bacteria appearing in the process of treatment and recovery and other conditions make the recurrence and metastasis of the tumor causing great harm again for patient.Photothermal therapy(PTT)has attracted considerable attention over passed few years owing to its novel minimal invasiveness.PTT converts light energy into heat energy through photothermal materials under the irradiation of laser,raising the local tissue temperature to kill cancer cells and bacteria.Unfortunately,most nano PTT agents have inherent defects such as non-degradable,difficult to modify the surface and low drug loading efficiency.Meanwhile,tumor microenvironment such as vascular malformation,high pressure of interstitial fluid and abundance in hydrogen peroxide diminish the targeting and bioavailability of nano PTT agents.All these factors have hindered PTT from further development.Therefore,the development of a new type of photothermal therapeutic agent with high photothermal conversion capability,minimally invasive,high drug loading efficiency that integrates the treatment of tumors and bacterial infections is very necessary to improve the efficiency of cancer treatment and alleviate the suffering of patients.In this research,we developed a novel iodine based hydrogel with photothermal conversion function.It effectively overcomes the shortcomings of low bioavailability,poor targeting and biotoxicity of nano PTT agents.The main contents and results of this dissertation are described in two parts as below:1)Firstly,a hydrogel system of low melting agar encapsulating starch and iodine complex nanoparticles(AM-I@Agar)was synthesized as a novel drug carrier for photothermal therapy of tumors and bacterial infections.In this hydrogel system,starch and iodine complex nanoparticles(AM-I NPs)were used as photothermal therapeutic agents due to their considerable near-infrared region absorption,photothermal conversion and biocompatibility.The low melting agar(Agar)was used as temperature-sensitive phase-change material to deliver drugs.When the infrared laser irradiated AM-I@Agar hydrogel,Agar would gradually liquefy and release iodide(I_n~-)as the temperature increases due to the photothermal conversion of AM-I NPs.After the release,I_n~-not only catalyze hydrogen peroxide to improve the hypoxic environment of tumors,but also kill bacteria to prevent bacterial infection.In this project,fluorouracil(5-FU)was chosen as chemotherapy drug buried in the AM-I@Agar hydrogel.The ability of AM-I/5-FU@Agar hydrogel to be used in PTT and chemotherapy to treat cancer and antibacterial was verified by mouse tumor and bacterial model.In the end,mouse tumor and bacteria experiments verified that AM-I/5-FU@Agar hydrogel as a new iodine-based PTT agent can effectively load drugs for the treatment of tumor and bacterial infections.2)Secondly,Polyvinyl alcohol-Boracic acid/Borax/Borate-Iodine(PVA-BBB-I)hydrogel was obtained by introducing I_n~-,through the hydrogen bond,into the hydrogel which was physical cross-linked between polyvinyl alcohol and borate ion.PVA-BBB-I hydrogel shows considerable absorption in the near-infrared region and great ability of photothermal conversion.Meanwhile,PVA-BBB-I hydrogel is temperature sensitivity.PVA-BBB-I hydrogel would melt and release I_n~-because the hydrogen bond cross-linking between polyvinyl alcohol and borate ions was destroyed with the increase of temperature.As a novel hydrogel with antibacterial and photothermal conversion functions,PVA-BBB-I hydrogel has immeasurable potential value in the photothermotherapy and chemotherapy synergy of cancer.