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<p>Implant-associated infections (IAIs) remain a major clinical challenge due to persistent bacterial biofilms and the establishment of a profoundly immunosuppressive microenvironment, which together hinder effective pathogen clearance and promote infection recurrence. Here, we report an ultrasound (US)-activated Bi@Bi-MOF nanoplatform that integrates efficient antibiofilm activity with immune reprogramming to achieve durable infection control without reliance on antibiotics. Upon US stimulation, Bi@Bi-MOF converts mechanical energy into localized electromechanical responses through its piezoelectric heterostructure, generating enhanced physicochemical stress that effectively disrupts mature methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) biofilms. This process leads to rapid bacterial inactivation and the release of immunogenic bacterial antigens, including bacterial DNA. Importantly, bacterial DNA derived from fragmented bacteria is efficiently internalized by dendritic cells (DCs) and gains access to the cytosolic compartment, thereby activating the cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) signaling pathway. This STING-dependent sensing promotes DC maturation, type I interferon production, and enhanced antigen processing and presentation. Consequently, Bi@Bi-MOF-mediated STING activation bridges innate and adaptive immunity, amplifying macrophage bactericidal functions and driving robust T cell and B cell responses. In a murine implant-associated MRSA infection model, this immunologically informed nanoplatform not only eradicates established infections but also establishes long-term immune memory, effectively protecting against bacterial reinfection. Collectively, this study demonstrates a non-antibiotic, US-triggered immunotherapeutic strategy in which piezoelectric conversion enables effective biofilm disruption and antigen release, thereby harnessing STING signaling to reprogram the infection microenvironment and prevent recurrent implant-associated infections.</p> Graphical Abstract <p></p>

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Ultrasound-activated piezoelectric Bi@Bi-MOF enables STING-mediated immunotherapy for implant-associated infections

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月19日

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  • Junkai Zeng,
  • Liang Chen,
  • Feihui Zeng,
  • Qunya Zheng,
  • Songye Wu,
  • Shengcan Li,
  • Shanhong Fang,
  • Hongbin Luo,
  • Deqing Hu,
  • Peng Chen

摘要

Implant-associated infections (IAIs) remain a major clinical challenge due to persistent bacterial biofilms and the establishment of a profoundly immunosuppressive microenvironment, which together hinder effective pathogen clearance and promote infection recurrence. Here, we report an ultrasound (US)-activated Bi@Bi-MOF nanoplatform that integrates efficient antibiofilm activity with immune reprogramming to achieve durable infection control without reliance on antibiotics. Upon US stimulation, Bi@Bi-MOF converts mechanical energy into localized electromechanical responses through its piezoelectric heterostructure, generating enhanced physicochemical stress that effectively disrupts mature methicillin-resistant Staphylococcus aureus (MRSA) biofilms. This process leads to rapid bacterial inactivation and the release of immunogenic bacterial antigens, including bacterial DNA. Importantly, bacterial DNA derived from fragmented bacteria is efficiently internalized by dendritic cells (DCs) and gains access to the cytosolic compartment, thereby activating the cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) signaling pathway. This STING-dependent sensing promotes DC maturation, type I interferon production, and enhanced antigen processing and presentation. Consequently, Bi@Bi-MOF-mediated STING activation bridges innate and adaptive immunity, amplifying macrophage bactericidal functions and driving robust T cell and B cell responses. In a murine implant-associated MRSA infection model, this immunologically informed nanoplatform not only eradicates established infections but also establishes long-term immune memory, effectively protecting against bacterial reinfection. Collectively, this study demonstrates a non-antibiotic, US-triggered immunotherapeutic strategy in which piezoelectric conversion enables effective biofilm disruption and antigen release, thereby harnessing STING signaling to reprogram the infection microenvironment and prevent recurrent implant-associated infections.

Graphical Abstract