{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T09:49:07Z","timestamp":1792316947839,"version":"4.4.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772159"],"award-info":[{"award-number":["81772159"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372272"],"award-info":[{"award-number":["82372272"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["and"],"award-info":[{"award-number":["and"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Cryptococcal meningitis (CM) is a significant global health issue, particularly affecting individuals with HIV. Amphotericin B (AmB) serves as the cornerstone treatment for CM; however, its clinical application is restricted due to limited penetration of the blood\u2013brain barrier and associated nephrotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study investigates the use of exosomes derived from induced pluripotent stem cells (iPSC-Exos) as carriers for AmB in treating CM, aiming to enhance therapeutic efficacy and safety and reduce AmB toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Exosomes were extracted from iPSC culture supernatants using ultrafiltration and ultracentrifugation. Their morphology and size were analyzed using transmission electron microscopy (TEM) and nanoparticle flow cytometry (nFCM). Purity was confirmed by Western blotting for markers CD9, CD63, and TSG101. AmB was loaded into iPSC-Exos using a co-incubation method. The cytotoxicity of the iPSC-Exo\/AmB complex was evaluated on HEK 293\u202fT and RAW264.7 cells using the CCK-8 assay, while apoptosis was assessed using live\/dead cell staining and flow cytometry. The hemolytic effects were tested using rabbit red blood cells. In a C57BL\/6\u202fJ mouse model of cryptococcal infection, treatment groups (AmB, iPSC-Exo\/AmB, and iPSC-Exo) were administered corresponding drugs, with blood and brain samples collected for analysis. The minimum inhibitory concentration (MIC) of iPSC-Exo\/AmB and conventional AmB against <jats:italic>Cryptococcus<\/jats:italic> was determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The iPSC-Exo\/AmB complex exhibited reduced cytotoxicity <jats:italic>in vitro<\/jats:italic> and decreased AmB-induced renal and hepatic toxicity <jats:italic>in vivo<\/jats:italic>. Its MIC against <jats:italic>Cryptococcus<\/jats:italic> was over eight times lower than conventional AmB, significantly reducing fungal burden in the mouse brain and lowering serum inflammatory factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The iPSC-Exo\/AmB complex is a promising therapeutic strategy that enhances AmB efficacy while reducing toxicity, offering new hope for treating CM and other refractory fungal infections of the central nervous system.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1531425","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T06:48:26Z","timestamp":1739170106000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["iPSC-derived exosomes as amphotericin B carriers: a promising approach to combat cryptococcal meningitis"],"prefix":"10.3389","volume":"16","author":[{"given":"Jingyu","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangjie","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiquan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guizhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julin","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s10020-024-00940-6","article-title":"Enhanced spinal cord repair using bioengineered induced pluripotent stem cell-derived exosomes loaded with miRNA","volume":"30","author":"Abbas","year":"2024","journal-title":"Mol. 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