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ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 16 - 2025 |
doi: 10.3389/fmicb.2025.1531425
This article is part of the Research Topic Emerging Antimicrobials: Sources, Mechanisms of Action, Spectrum of Activity, Combination Antimicrobial Therapy, and Resistance Mechanisms View all 8 articles
iPSC-Derived Exosomes as Carriers for Amphotericin B: A Promising Approach to Combat Cryptococcal Meningitis
Provisionally accepted- 1 Third Affiliated Hospital of Naval Medical University, Shanghai, China
- 2 Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
- 3 Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, Shanghai, China
- 4 Shanghai Tenth People's Hospital, Tongji University, Shanghai, Shanghai Municipality, China
Background: 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-brain barrier and associated nephrotoxicity.Objective: 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 while reducing AmB toxicity. Methods: Exosomes were extracted from iPSC culture supernatants using ultrafiltration and ultracentrifugation. Their morphology and size were analyzed via 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 293T and RAW264.7 cells with the CCK-8 assay, while apoptosis was assessed using live/dead cell staining and flow cytometry. Hemolytic effects were tested with rabbit red blood cells. In a C57BL/6JC57BL/6 mouse model of cryptococcal infection, treatment groups (AmB, iPSC-Exo/AmB, and iPSC-Exo) received corresponding drugs, with blood and brain samples collected for analysis. The minimum inhibitory concentration (MIC) of iPSC-Exo/AmB and conventional AmB against Cryptococcus was determined.The iPSC-Exo/AmB complex exhibited reduced cytotoxicity in vitro and decreased AmBinduced renal and hepatic toxicity in vivo. Its MIC against Cryptococcus was over eight times lower than conventional AmB, significantly reducing fungal burden in the mouse brain and lowering serum inflammatory factors.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.
Keywords: Cryptococcus neoformans, Cryptococcal meningitis, Amphotericin B, Induced Pluripotent Stem Cells, Drug Delivery Systems
Received: 20 Nov 2024; Accepted: 20 Jan 2025.
Copyright: © 2025 Zhao, Fang, Gao, Chen, Wang and Gu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Julin Gu, Third Affiliated Hospital of Naval Medical University, Shanghai, China
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