Sonocatalytic oncolysis microbiota curb intrinsic microbiota lactate metabolism and blockade CD24-Siglec10 immune escape to revitalize immunological surveillance

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Intrinsic lactate retention of chemically- or genetically-engineered bacteria therapy aggravates tumor immunosuppression, which will collaborate with immune escape to cause immunological surveillance failure. To address them, sonocatalytic oncolysis Escherichia coli (E.coli) that chemically chelated anti-CD24 and TiO1+x have been engineered to blockade CD24-siglec10 interaction, regulate microbiota colonization and curb its lactate metabolism, which are leveraged to revitalize immunological surveillance and repress breast cancer. The chemically-engineered E.coli inherited their parent genetic information and expansion function. Therefore, their intrinsic hypoxia tropism and CD24 targeting allow them to specifically accumulate and colonize in solid breast cancer to lyse tumor cells. The conjugated CD24 antibody is allowed to blockade CD24-Siglec10 signaling axis and revitalize immunological surveillance. More significantly, the chelated TiO1+x sonosensitizers produce ROS to render bacteria expansion controllable and curb immunosuppression-associated lactate birth that are usually neglected. Systematic experiments successfully vlaidate hypoxia-objective active targeting, sonocatalytic therapy, microbiota expansion-enabled oncolysis, CD24-Siglec10 communication blockade and precise microbiota abundance & lactate metabolism attenuations. These actions contribute to the potentiated anti-tumor immunity and activated anti-metastasis immune memory against breast cancer development. Our pioneering work provide a route to sonocatalytic cancer immunotherapy.