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

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机构: [1]Department of Ultrasound and Central Laboratory, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, PR China [2]Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, No. 301 Yan-chang-zhong Road, Shanghai, 200072, PR China [3]Department of Ultrasound, Zhongshan Hospital, Institute of Ultrasound in Medicine and Engineering, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, PR China
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关键词: Sonocatalytic oncolysis microbiota CD24-Siglec10 signaling axis Microbiota lactate metabolism curbing Immunological surveillance Immune memory

摘要:
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.Copyright © 2024. Published by Elsevier Ltd.

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大类 | 1 区 医学
小类 | 1 区 工程:生物医学 1 区 材料科学:生物材料
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Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS

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第一作者机构: [1]Department of Ultrasound and Central Laboratory, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Second Section, First Ring Road, Chengdu, 610072, Sichuan, PR China
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