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Here, we demonstrate that rigid hollow microparticles enable controlled, targeted thermal treatments of deep tissues via FUS. These acoustically responsive agents exhibit properties comparable to microbubbles yet possess superior mechanical stability, prolonged circulation, and enhanced responsiveness. Characterized by a negative acoustic contrast factor, the hollow microparticles amplify FUS\u2010induced effects\u2014particularly localized hyperthermia\u2014enabling precise, robust, and controllable thermal therapy. Tissue ablation experiments under optoacoustic imaging guidance demonstrate strong responsiveness to FUS, with histological analyses confirming a threefold increase in ablation volume compared with microparticle\u2010free controls. Experimental and numerical results indicate that this enhanced efficacy arises from first\u2010order acoustic effects and secondary mechanisms, including acoustic scattering and stable particle\u2010to\u2010particle interactions. Unlike microbubbles, hollow microparticles rely on non\u2010cavitational heating, enabling predictable, dose\u2010dependent thermal responses that improve safety and efficacy. The frequency\u2010dependent response further highlights their multifunctional potential under varying acoustic conditions. These findings establish rigid hollow microparticles as stable, versatile acoustic agents that significantly advance the therapeutic scope and clinical utility of FUS therapies.<\/jats:p>","DOI":"10.1002\/advs.202512337","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T06:12:36Z","timestamp":1766470356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rigid Hollow Microparticles for Enhanced Focused Ultrasound Treatment Under Optoacoustic Guidance"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-4624","authenticated-orcid":false,"given":"Nima","family":"Mahkam","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology Faculty of Medicine University of Zurich  Zurich Switzerland"},{"name":"Physical Intelligence Department Max Planck Institute for Intelligent Systems  Stuttgart Germany"},{"name":"Institute for Biomedical Engineering Department of Information Technology and Electrical Engineering ETH Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology Faculty of Medicine University of Zurich  Zurich Switzerland"},{"name":"Institute for Biomedical Engineering Department of Information Technology and Electrical Engineering ETH Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor","family":"Estrada","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology Faculty of Medicine University of Zurich  Zurich Switzerland"},{"name":"Institute for Biomedical Engineering Department of Information Technology and Electrical Engineering ETH Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananya","family":"Amitabh","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering Department of Information Technology and Electrical Engineering ETH Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4301-4053","authenticated-orcid":false,"given":"Amirreza","family":"Aghakhani","sequence":"additional","affiliation":[{"name":"Institute of Biomaterials and\u00a0Biomolecular Systems University of Stuttgart  Stuttgart Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8249-3854","authenticated-orcid":false,"given":"Metin","family":"Sitti","sequence":"additional","affiliation":[{"name":"School of Medicine Ko\u00e7 University  Istanbul Turkey"},{"name":"College of Engineering Ko\u00e7 University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8676-0964","authenticated-orcid":false,"given":"Daniel","family":"Razansky","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology Faculty of Medicine University of Zurich  Zurich Switzerland"},{"name":"Institute for Biomedical Engineering Department of Information Technology and Electrical Engineering ETH Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00418-z"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.76199"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2022.01.014"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol30050377"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9020460"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-023-04492-3"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-024-06413-9"},{"key":"e_1_2_10_9_1","first-page":"139","article-title":"Nonthermal Ablation in the Rat Brain Using Focused Ultrasound and an Ultrasound Contrast Agent: Long\u2010term Effects","volume":"176","author":"Brokowski A. 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