Effect Of Ganoderma Lucidum Polysaccharide Conjugated Bismuth Sulfide Nanopartides In Combination With Radioimmunothcrapy And Anti-tumor

Radiotherapy is a traditional method for cancer therapy,but may become ineffective likely due to the radiation-induced immunosuppression.Other than simply increasing the radiation dose,reactivation of immunosuppression in the tumor microenvironment is an alternative strategy for successful cancer treatment.In this work,we synthesized bismuth sulfide nanoparticles(BiNP)and conjugated with immunoactivity Ganoderma lucidum polysaccharide(GLP).GLP-BiNP were able to increase the sensitivity of radiotherapy,attributing to the efficient X-ray absorption of bismuth element.BiNP alone can mildly activate dendritic cells(DC)in vitro,while GLP-BiNP further enhanced the level of DC maturation,shown as the increase in phenotypic maturation markers,cytokine release,acid phosphatase activity,and T cell proliferation in DC/T cell co-culture.GLP-BiNP altered the tissue distribution compared to BiNP,with faster accumulation in the tumor.In the meanwhile,mature DC greatly increased in both tumor and spleen by GLP-BiNP within 24 h.GLP-BiNP combination with radiation achieved remarkable inhibition on tumor growth through apoptosis.Alternatively,lung metastasis was largely prohibited by GLP-BiNP,shown as reduced amount of tumor nodules and cancer cell invasion by pathological findings.Mechanistically,GLP-BiNP altered the tumor immunosuppression microenvironment by preferably increasing the number of intra-tumor CD8+T cell proliferation,as well as the improved immunobalance shown as the increased serum IFN-y/IL-4 ratio.Specifically,GLP conjugating seemed to protect kidney from injury occasionally introduced by bare BiNP.As the result,GLP-BiNP play a dual role on the tumor treatment through radiosensitization and immunoactivities.