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| Status |
Public on Sep 18, 2024 |
| Title |
Biodegradable oxygen-evolving metalloantibiotics for spatiotemporal sono-metalloimmunotherapy against orthopaedic biofilm infections |
| Organisms |
Staphylococcus aureus; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pathogen-host competition for manganese and intricate immunostimulatory pathways severely attenuates the efficacy of antibacterial immunotherapy against biofilm infections associated with orthopaedic implants. Herein, we introduce an unprecedented spatiotemporal sono-metalloimmunotherapy (SMIT) strategy aimed at efficient biofilm ablation by custom design of ingenious biomimetic metal-organic framework (PCN-224)-coated MnO2-hydrangea nanoparticles (MnPM) as a metalloantibiotic. Upon reaching the acidic H2O2-enriched biofilm microenvironment, MnPM can convert abundant H2O2 into oxygen, which is conducive to significantly enhancing the efficacy of ultrasound (US)-triggered sonodynamic therapy (SDT), thereby exposing bacteria-associated antigens (BAAs). Moreover, MnPM disrupts bacterial homeostasis, further killing more bacteria. Then, the Mn ions released from the degraded MnO2 can recharge immune cells to enhance the cGAS-STING signaling pathway sensing of BAAs, further boosting the immune response and suppressing biofilm growth via biofilm-specific T cell responses. Following US withdrawal, the sustained oxygenation promotes the survival and migration of fibroblasts, stimulates the expression of angiogenic growth factors and angiogenesis, and neutralizes excessive inflammation. Our findings highlight that MnPM may act as an immune costimulatory metalloantibiotic to regulate the cGAS-STING signaling pathway, presenting a promising alternative to antibiotics for orthopaedic biofilm infection treatment and pro-tissue repair.
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| Overall design |
We used Staphylococcus aureus as a study subject. The intervened bacteria were obtained through different studied nanomaterials and sequenced for transcriptomics.
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| Contributor(s) |
Su Z, Xu D, Hu X, Zhu W, Kong L, Qian Z, Mei J, Ma R, Shang X, Fan W, Zhu C |
| Citation(s) |
39277594 |
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| Submission date |
Mar 06, 2024 |
| Last update date |
Sep 18, 2024 |
| Contact name |
Wanbo Zhu |
| Organization name |
Shanghai Sixth Peoples Hospital Affiliated to Shanghai Jiao Tong University
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| Street address |
No600, Yishan road, Shanghai, China
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| City |
Shanghai |
| State/province |
None Selected |
| ZIP/Postal code |
200233 |
| Country |
China |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL27158 |
Illumina NovaSeq 6000 (Staphylococcus aureus) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA1084754 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE260971_Processed_data.txt.gz |
268.8 Kb |
(ftp)(http) |
TXT |
| GSE260971_Processed_data.xlsx |
1.1 Mb |
(ftp)(http) |
XLSX |
| GSE260971_counts.txt.gz |
157.0 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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