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However, conventional management after CIRI exhibits numerous limitations.Transcranial low-intensity ultrasound stimulation (TLUS) has been extensively utilized in the field of neuromodulation owing to its characteristics of zero potential side effects, noninvasiveness, deep tissue penetration, and precise spatial targeting capability. Here, we develop a smart multifunctional ultrasound-responsive delivery system to regulate CIRI. Briefly, curcumin, a well-documented safe neuroprotective monomer derived from traditional Chinese medicine, is encapsulated into self-assembled liposomal nanocarriers (RRP@Lipo-Cur). These nanocarriers are modified with reactive oxygen species- and ultrasound-responsive functional elements, as well as neuron-targeting peptides, enabling targeted accumulation in ischemic penumbra and stimuli-responsive drug release. In the mouse model of middle cerebral artery occlusion\/reperfusion (MCAO\/r), the synergistic treatment of RRP@Lipo-Cur and TLUS significantly facilitated the polarization of microglia from the M1 to the M2 phenotype via the intracellular mitogen-activated protein kinase (MAPK) and nuclear factor \u03baB signaling (NF-\u03baB) pathways, which effectively promoted the establishment of an anti-inflammatory microenvironment in the ischemic penumbra, thereby providing neuroprotection for the damaged neurons. Furthermore, in comparison to single nanomaterial or TLUS interventions, synergistic treatment can optimally modulate neuroinflammation, safeguard injured neurons, and enhance the recovery of neurological function.<\/jats:p>","DOI":"10.34133\/research.0861","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T05:00:01Z","timestamp":1754542801000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":5,"title":["Synergistic Therapeutic Platform Combining Transcranial Low-Intensity Ultrasound Stimulation and Curcumin Load Liposome Ameliorates Cerebral Ischemia by Modulating Microglia Polarization-Mediated Neuroinflammatory Microenvironment"],"prefix":"10.34133","volume":"8","author":[{"given":"Haocheng","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Rehabilitation, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of \rZhengzhou University, Zhengzhou University, Zhengzhou, Henan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengkun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengran","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijian","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, \rThe Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0524-9951","authenticated-orcid":true,"given":"Zhiwen","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, \rThe Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, China."},{"name":"Department of Sports Medicine, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, Huashan Hospital, \rFudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"issue":"5","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1161\/STROKEAHA.122.040073","article-title":"Projected global trends in ischemic stroke incidence, deaths and disability-adjusted life years from 2020 to 2030","volume":"54","author":"Pu L","year":"2023","unstructured":"Pu L, Wang L, Zhang R, Zhao T, Jiang Y, Han L. 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