Preparation Of Transferrin-modified Cobalt Ferrate Nanoparticles And Application In The Chemodynamic-photothermal Synergistic Antitumor Study

Tumor is an important disease that endangers human health.Traditional treatments（radiotherapy,surgery,chemotherapy）are highly traumatic and have many complications,while the indiscriminate attack of drugs on normal cells can cause huge side effects that bring great pain to patients.Nanomedicines based on the tumor microenvironment（TEM）have high tumor tissue penetration and retention effects,which can improve their specific uptake by tumor cells and thus enhance the effectiveness and safety of tumor treatment.Novel antitumor nanomedicine treatment methods include chemodynamic therapy,photothermal therapy,and acoustic dynamics therapy,but they are limited by low enrichment in tumor sites,uneven distribution and poor efficacy of single therapy.In order to achieve safe and efficient precision tumor therapy,this thesis proposes a transferrin-targeted modified cobalt ferrate nanoparticle to realize a synergistic photothermal and chemokinetic precision tumor treatment strategy.In the first part,the construction of transferrin-modified ferric acid nanoparticles（Co Fe₂O₄@Tf,CFOT）and characterization of properties and performance.Firstly,cobalt ferrate nanoparticles（Co Fe₂O₄,CFO）were synthesized in one step by solvent thermal method using polyethylene glycol derivative m-PEG-P（AGE-MPA）as stabilizer,and then Co Fe₂O₄@Tf（CFOT）composite nanoparticles were synthesized by chelation of transferrin（Tf）with metal ions.The CFOT nanoparticles were characterized by XRD,FTIR,XPS,TEM,zeta potential and DLS,which demonstrated the high crystallinity,small particle size（63.10±12.59 nm）,good dispersion and high negative charge（-22.8 m V）,good stability and water solubility of CFOT nanoparticles.The nanoparticles have good photothermal conversion efficiency of 46.5%and good photothermal stability under 808 nm laser irradiation.In addition,methylene blue（MB）degradation experiments and EPR experiments demonstrated the excellent chemical kinetic properties of CFOT.In the second part,CFOT nanoparticles were used for tumor precision therapy through synergistic photothermal/chemokinetic therapy.Firstly,the in vitro anti-tumor activity of CFOT was evaluated by cellular assays.the survival rate of human hepatocytes（L-O2）and human umbilical vein epithelial cells（HUVEC）under the effect of CFOT in MTT assay was higher than 80%,indicating that CFOT is less toxic to normal cells and has excellent biocompatibility and safety.In the cell uptake assay and the in vivo ion distribution assay of H22 transplanted tumor mice,CFOT nanoparticles accumulated more in liver cancer cells（H22,Hep G2）and H22 tumor tissues,reflecting the excellent tumor-specific targeting of CFOT nanoparticles.The MTT assay on hepatocellular carcinoma cells,Annexin V-FITC-PI apoptosis flow assay,and Calcein-AM/PI double-stained cell assay resulted in more than85%hepatocellular carcinoma cell death under laser irradiation,and its tumor cell killing effect was superior to that of CFO without Tf modification.further conducted H22transplantation tumor Balb/c mouse model treatment experiments demonstrated that the synergistic photothermal/chemical kinetic precision treatment strategy of CFOT has excellent therapeutic effects and can effectively cure transplanted mouse liver cancer tumors.In conclusion,this study successfully synthesized transferrin-modified CFOT nanoparticles,which have good photothermal and chemical kinetic properties,superior biosafety and clear tumor targeting,and can significantly inhibit the growth of transplanted H22 tumors in vivo under the synergistic effect of photothermal-chemical kinetic therapy.This topic can provide a new therapeutic tool for the treatment of liver cancer.