Development Of Manganese Phosphate Nanomaterials For Theranostics Of The Osteosarcoma

Osteosarcoma is the most common primary malignant tumor in children and young adults.Osteosarcoma is highly metastatic and highly recurrent,with a survival rate of less than 30%in recurrent patients.The existing treatment methods mainly include surgery,chemotherapy,and radiotherapy.Single surgery has a high risk of metastasis,while chemotherapy can cause drug resistance,and high-dose chemotherapy drugs can cause serious side effects.Osteosarcoma is less sensitive to radiation therapy.New therapeutics such as immunotherapy,photodynamic therapy,and photothermal therapy are also emerging into the field of anti-osteosarcoma,but have not yet achieved good results.In the past 30 years,no breakthrough has been made in the treatment of osteosarcoma.Therefore,osteosarcoma treatment still urgently requires effective treatment to improve the treatment effect.Manganese is an essential element of life,and Mn2+ ion has cytotoxicity,which has farreaching significance for the treatment of tumors.Based on Mn2+ ion cytotoxicity and paramagnetism,this study developed a new method to treat osteosarcoma,in order to reduce chemotherapy-related side effects.Manganese phosphate(MnP)material has been used,as an anticancer drug in the therapy of osteosarcoma.Meantime,the paramagnetism of Mn2+gives it magnetic resonance imaging(MRI)properties and can be used as a T1-MRI contrast agent to diagnose and monitor changes in the cancerous site of osteosarcoma.In this thesis,polyacrylic acid(PAA)was doped into MnP by a chemical precipitation method,and PAA-Mn3(PO4)2·3H2O(PAA-manganese phosphate)and PAA-AMP(PAAamorphous manganese phosphate,PAA-AMP)were successfully prepared by adjusting the order of dropping of ammonia water and manganese nitrate.In order to enhance the targeting to cancer cells,Folic acid(FA)ligands were grafted to prepare FA-PAA-Mn3(PO4)2·3H2O and FA-PAA-AMP nanomaterials.Moreover,the magnetic resonance imaging properties of PAA-Mn3(PO4)2-3H2O and PAA-AMP were detected in an in vitro environment,and the r1 values were 6.75 mM-1 s-1 and 6.65 mM-1 s-1 respectively,which proved that PAAMn3(PO4)2·3H2O and PAA-AMP had higher r1 relaxation rate and imaging function.The antiosteosarcoma properties of PAA-Mn3(PO4)2·3H2O,PAA-AMP,FA-PAA-Mn3(PO4)2·3H2O and FA-PAA-AMP were analyzed by morphological observation,live/dead cell staining and CCK-8 cytotoxicity test.The results show that FA-PAA-AMP can kill osteosarcoma cells rapidly and effectively,which is likely used as a diagnostic and therapeutic agent for osteosarcoma treatment in future.