E.coli Developed Precious Metal Nanoparticles By Reduction Method For Malignant Melanoma Treatment

Malignant melanoma is one of the tumors with high clinical mortality.Single cancer treatment such as PTT and CDT are not enough to completely cure malignant melanoma.In addition,immune checkpoint inhibitors are not effective on the treatment of all types of tumors.In "cold" tumors that lack immune cell infiltration,including melanoma,glioblastoma,and prostate cancer,their therapeutic effects are limited.BL21(DE3)E.coli can reduce metal nanoparticles in situ on its surface through its own metabolic process,and its cell wall intrinsic component lipopolysaccharide(LPS)can activate the body's adaptive immunity to facilitate immune infiltration.Therefore,to address above problem,two kinds of combination therapy strategies based on BL21(DE3)E.coli were designed to treat malignant melanoma.1.E.coli Decorated with Au/Pt Nanoparticles Were Developed for Combination Chemodynamic and Immunity Therapy of Malignant MelanomaThe synergistic treatment strategy of chemodynamic therapy combined with PD-L1 immunity inhibitor can overcome the shortcomings of insufficient effect in monotherapy,meanwhile,E.coli can promote the treatment efficacy of PD-L1 inhibitors.As a result,the combination treatment not only achieve inhibition of malignant melanoma but also increase mice survival rate.In the tumor acid environment,gold and platinum nanoparticles decorated on Bac-Au@Pt can catalyze the production of singlet oxygen and superoxide anion,thereby inducing lipid peroxidation of cancer cell membranes,causing cancer cells to enter the process of iron death and apoptosis.Bac-Au@Pt can achieve the purpose of killing cancer cells to treat cancer when combined with anti-PD-L1.In addition,genomics analysis of melanoma after combination therapy showed that Bac-Au@Pt can enhance the body's immune level and promote the efficacy of PD-L1 immunosuppressants.2.Biogenic Hybrid Nanosheets Were Developed for Combination Photothermal and Immunity Therapy of Malignant MelanomaAu MNs meterial based on E.coli was designed and prepared to treated melanoma with photothermal therapy combined with PD-L1 inhibitor immunotherapy strategy.Au MNs meterial eliminate bacterial contents,reduce bacterial toxicity and side effects on the body.After melanoma enriches Au MNs by EPR effect,the photothermal conversion caused by the plasma coupling effect is generated under the light of 808 nm near-infrared laser in the melanoma to achieve the local temperature rise of the body.Au MNs can achieve the purpose of malignant melanoma in mice when combined with PD-L1 inhibitors.Flow cytometry analysis of CD3,CD4,and CD8 immune cells in tumor sections showed that Au MNs conbined with anti-PD-L1 can increase the body's level of CD4 immune cells.