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Anti-ferroptosis exosomes engineered for targeting M2 microglia to improve neurological function in ischemic stroke.
Wang, Yong; Liu, Zhuohang; Li, Luyu; Zhang, Zengyu; Zhang, Kai; Chu, Min; Liu, Yang; Mao, Xueyu; Wu, Di; Xu, Dongsheng; Zhao, Jing.
Afiliación
  • Wang Y; Department of Neurology, Minhang Hospital, Fudan University, Shanghai, 201100, China.
  • Liu Z; Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, 200030, China.
  • Li L; Department of Neurology, Minhang Hospital, Fudan University, Shanghai, 201100, China.
  • Zhang Z; Department of Dermatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200001, China.
  • Zhang K; Department of Neurology, Minhang Hospital, Fudan University, Shanghai, 201100, China.
  • Chu M; Department of Cardiovascular Medicine, Pujiang Traditional Chinese Medicine Hospital, Zhejiang, 322200, China.
  • Liu Y; Department of Neurology, Minhang Hospital, Fudan University, Shanghai, 201100, China.
  • Mao X; Department of Neurology, Minhang Hospital, Fudan University, Shanghai, 201100, China.
  • Wu D; Department of Neurology, Minhang Hospital, Fudan University, Shanghai, 201100, China.
  • Xu D; Department of Neurology, Minhang Hospital, Fudan University, Shanghai, 201100, China.
  • Zhao J; College of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 200120, China.
J Nanobiotechnology ; 22(1): 291, 2024 May 27.
Article en En | MEDLINE | ID: mdl-38802919
ABSTRACT

BACKGROUND:

Stroke is a devastating disease affecting populations worldwide and is the primary cause of long-term disability. The inflammatory storm plays a crucial role in the progression of stroke. In the acute phase of ischemic stroke, there is a transient increase in anti-inflammatory M2 microglia followed by a rapid decline. Due to the abundant phospholipid in brain tissue, lipid peroxidation is a notable characteristic of ischemia/reperfusion (I/R), constituting a structural foundation for ferroptosis in M2 microglia. Slowing down the decrease in M2 microglia numbers and controlling the inflammatory microenvironment holds significant potential for enhancing stroke recovery.

RESULTS:

We found that the ferroptosis inhibitor can modulate inflammatory response in MCAO mice, characterizing that the level of M2 microglia-related cytokines was increased. We then confirmed that different subtypes of microglia exhibit distinct sensitivities to I/R-induced ferroptosis. Adipose-derived stem cells derived exosome (ADSC-Exo) effectively decreased the susceptibility of M2 microglia to ferroptosis via Fxr2/Atf3/Slc7a11, suppressing the inflammatory microenvironment and promoting neuronal survival. Furthermore, through plasmid engineering, a more efficient M2 microglia-targeted exosome, termed M2pep-ADSC-Exo, was developed. In vivo and in vitro experiments demonstrated that M2pep-ADSC-Exo exhibits significant targeting specificity for M2 microglia, further inhibiting M2 microglia ferroptosis and improving neurological function in ischemic stroke mice.

CONCLUSION:

Collectively, we illustrated a novel potential therapeutic mechanism that Fxr2 in ADSC-Exo could alleviate the M2 microglia ferroptosis via regulating Atf3/Slc7all expression, hence inhibiting the inflammatory microenvironment, improving neurofunction recovery in cerebral I/R injury. We obtained a novel exosome, M2pep-ADSC-Exo, through engineered modification, which exhibits improved targeting capabilities toward M2 microglia. This provides a new avenue for the treatment of stroke.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microglía / Exosomas / Ferroptosis / Accidente Cerebrovascular Isquémico / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: J Nanobiotechnology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Microglía / Exosomas / Ferroptosis / Accidente Cerebrovascular Isquémico / Ratones Endogámicos C57BL Límite: Animals Idioma: En Revista: J Nanobiotechnology Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido