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Pyroptotic-Spatiotemporally Selective Delivery of siRNA against Pyroptosis and Autoimmune Diseases.
Pan, Zongyou; Xu, Kaiwang; Huang, Guanrui; Hu, Haoran; Yang, Huang; Shen, Haotian; Qiu, Kaijie; Wang, Canlong; Xu, Tengjing; Yu, Xinning; Fang, Jinhua; Wang, Jiajie; Lin, Yunting; Dai, Jiacheng; Zhong, Yuting; Song, Hongyun; Zhu, Sunan; Wang, Siheng; Zhou, Zhuxing; Sun, Chuyue; Tang, Zhaopeng; Liao, Shiyao; Yang, Guang; You, Zhiyuan; Dai, Xuesong; Mao, Zhengwei.
Afiliação
  • Pan Z; Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • Xu K; Orthopedics Research Institute, Zhejiang University, Hangzhou, 310009, China.
  • Huang G; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China.
  • Hu H; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, China.
  • Yang H; Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
  • Shen H; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Qiu K; Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • Wang C; Orthopedics Research Institute, Zhejiang University, Hangzhou, 310009, China.
  • Xu T; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China.
  • Yu X; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, China.
  • Fang J; Department of Orthopedic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • Wang J; Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, 999077, China.
  • Lin Y; Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • Dai J; MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China.
  • Zhong Y; Department of Orthopedic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • Song H; Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • Zhu S; Orthopedics Research Institute, Zhejiang University, Hangzhou, 310009, China.
  • Wang S; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China.
  • Zhou Z; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, China.
  • Sun C; Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • Tang Z; Orthopedics Research Institute, Zhejiang University, Hangzhou, 310009, China.
  • Liao S; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China.
  • Yang G; Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, 310009, China.
  • You Z; Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • Dai X; Orthopedics Research Institute, Zhejiang University, Hangzhou, 310009, China.
  • Mao Z; Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, 310009, China.
Adv Mater ; : e2407115, 2024 Jul 30.
Article em En | MEDLINE | ID: mdl-39081086
ABSTRACT
Small-interfering RNAs (siRNAs) offer promising prospects for treating pyroptosis-related autoimmune diseases. However, poor stability and off-target effects during in vivo transportation hinder their practical clinical applications. Precision delivery and adaptive release of siRNAs into inflamed tissues and immune cells could unleash their full therapeutic potential. This study establishes a pyroptotic-spatiotemporally selective siRNA delivery system (PMRC@siGSDME) that selectively targets inflammatory tissues, responds to pyroptosis, and exhibits remarkable therapeutic efficacy against various autoimmune diseases. Novel hybrid nanovesicles (NVs) are designed as a combination of pyroptotic macrophage membranes (PMs) and R8-cardiolipin-containing nanovesicles (RC-NVs). Evidence provides that PM-derived proteins involved in cell-cell interactions and membrane trafficking may contribute to the specificity of NVs to inflammatory tissue. In addition, cardiolipin anchored in the hybrid NVs increases its affinity for activated gasdermin E (GSDME) and achieves pyroptosis-adaptive release of siGSDME for the spatiotemporally selective suppression of immune responses. More importantly, PMRC@siGSDME displays significant anti-inflammatory and therapeutic effects in multiple mouse autoimmune disease models, including arthritis and inflammatory bowel disease (IBD). Collectively, an innovative siRNA delivery strategy precisely tailored for pyroptotic cells has been developed, paving the way for new treatments for autoimmune inflammatory diseases with minimal side effects and wide clinical applicability.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Adv Mater Assunto da revista: BIOFISICA / QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Alemanha
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Adv Mater Assunto da revista: BIOFISICA / QUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Alemanha