Acoustic vortex tweezers selectively manipulated intelligent microbots to achieve in situ explosive antibody production for precise immunotherapy

Acoustic vortex tweezers selectively manipulated intelligent microbots to achieve in situ explosive antibody production for precise immunotherapy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Acoustic vortex tweezers selectively manipulated intelligent microbots to achieve in situ explosive antibody production for precise immunotherapy Zhen Ya, Haitao Wu, Wanlin Jia, Yan Li, Mingting Zhu, Lei Zhang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7968444/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Immune checkpoint blockade (ICB)-based immunotherapy is limited by its poor tumor targeting and rapid clearance of antibodies. Here, we developed the acoustic vortex (AV) tweezers that actively aggregated microbots for spatiotemporally controlled in situ explosive anti-PD-L1 production to achieve localized ICB-based immunotherapy. Engineered bacteria were conjugated with multifunctional nanoparticles combining chemotherapy, sonodynamic therapy, and plasmid-encoded anti-PD-L1, forming microbots capable of ultrasound-mediated aggregation and deep tumor penetration. AV tweezers with a larger annular focal region compared with conventional ultrasound, actively induced microbot aggregation in tumor-associated vasculature, while mild hyperthermia triggered expression and secretion of IFN-γ, promoting M2-to-M1 macrophage polarization. The release of DOX and Ce6 induced immunogenic cell death, synergistically enhancing anti-tumor responses. The localized antibody production factory achieved high intratumoral anti-PD-L1 level while limiting systemic exposure, thereby overcoming major limitations of conventional ICB therapy. Hence, this strategy established a programmable and dual-targeting platform for precise tumor immunotherapy. Biological sciences/Biotechnology/Biomaterials/Drug delivery Biological sciences/Biotechnology/Gene delivery/Transfection Full Text Additional Declarations There is NO Competing Interest. All animal experiments were performed under the approved guidelines of the Animal Experiment Ethics Committee of the School of Life Science and Technology, Xi’an Jiaotong University (XJTUBME-202415). Supplementary Files Supplementaryfile.docx Supplementary file Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7968444","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":537038873,"identity":"432822f2-ba8d-4ae2-a7ac-f583be0c385c","order_by":0,"name":"Zhen 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Here, we developed the acoustic vortex (AV) tweezers that actively aggregated microbots for spatiotemporally controlled in situ explosive anti-PD-L1 production to achieve localized ICB-based immunotherapy. Engineered bacteria were conjugated with multifunctional nanoparticles combining chemotherapy, sonodynamic therapy, and plasmid-encoded anti-PD-L1, forming microbots capable of ultrasound-mediated aggregation and deep tumor penetration. AV tweezers with a larger annular focal region compared with conventional ultrasound, actively induced microbot aggregation in tumor-associated vasculature, while mild hyperthermia triggered expression and secretion of IFN-γ, promoting M2-to-M1 macrophage polarization. The release of DOX and Ce6 induced immunogenic cell death, synergistically enhancing anti-tumor responses. 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