Hemoglobin-based Nanomedicines For Tumor Therapy

Protein is an important part of the organism.It has the characteristics of good biocompatibility,no immunogenicity,definite degradation pathway,etc.Hemoglobin is one of the most valuable proteins in recent years.Based on the structural characteristics of hemoglobin and its multifunctional functions such as oxygen supply and targeting,the development of hemoglobin based nanodrugs and the study of its anti-tumor therapy provide a new idea to deal with the problems such as insufficient tissue penetration of photosensitizer in current photodynamic therapy and complex tumor immune microenvironment.(1)Hemoglobin-based nano nanomedicines for targeted immunotherapy and chemotherapy of tumor:process repeat Hb-DOXM@Cel,spherical or sphere-like micelles with average particle size of 126 nm;The drug loading of adriamycin was 3.85%and celecoxib 3.46%.Doxorubicin and celecoxib are released rapidly under acidic conditions.Mechanism of action:Protein immunoblotting was used to verify the binding of hemoglobin to binding globin.MTT colorimetric assay demonstrated that erythroalbumin and bound globin complex could specifically target M2-type macrophages.Immunohistochemical analysis showed that a large number of CD 163 receptors were expressed on macrophages of tumor tissue in the mouse model.Fluorescence imaging results showed that the hemoglobin-bound globin complex targeted M2 macrophages.According to immunofluorescence and immunohistochemical analysis,celecoxib can inhibit cyclooxygenase and reduce prostaglandin E2.Efficacy evaluation of mouse liver cancer(H22):After treatment,the weight and volume of tumors in the target drug treatment group were the smallest compared with the control drug.Efficacy evaluation of mouse breast cancer(4T1)lung metastasis model:After treatment,compared with control drug,the tumor inhibition rate of target drug treatment group was 79.97%;Flow cytometry detected the least amount of tumor cells and M2-type macrophages,and observed the least amount of tumor cell nucleus density in lung.Flow cytometry detected the most T cell infiltration.The survival time of mice was significantly prolonged.Safety evaluation:No significant pathological changes were observed in the animal model after treatment with the target drug through monitoring of body weight and liver function parameters,observation of viscera tissues and immunohistochemical analysis of maj or viscera macrophages.(2)Hemoglobin-based nano nanomedicines for spontaneous photodynamic therapy of tumor:spherical or quasi-spherical nanoparticles with an average particle size of 111.7 nm Hb@Ce6-Lum were prepared,the drug loading of Ce6 was 2.48%,the particle size distribution was uniform,and the PDI was all below 0.250.Efficacy evaluation:Hb@Ce6-Lum,the ROS release of the nano-drug was the highest compared with the contrast drug.HeLa and 4T1 cells showed the strongest antitumor activity.The drug endocytosis was the highest in HeLa cells at 4 h.Based on the structure and functional characteristics of hemoglobin,the construction of hemoglobin-based nano drugs,with controllable quality,has specific tumor targeting,oxygen supply,catalysis and other functions,and can be used in the combination therapy of photodynamic therapy,chemotherapy and immunotherapy.More specific functions of hemoglobin are being explored,and it is expected to develop more other biological functions of hemoglobin,such as the carrier of various gases,peroxidase catalysts and macrophage targeting ligand,for the treatment of a variety of other diseases.