Carbon dot-based treatment for bacterial pneumonia by promoting a PI3K-mediated M1 polarization of macrophages
Abstract As the incessant emergence of drug-resistant bacterial strains, bacterial pneumonia poses a serious threat to the public health worldwide. There is an urgent need to explore unconventional therapeutic strategies. Carbon dots are usually designed to directly kill bacteria, however, carbon do...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03399-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850173069469941760 |
|---|---|
| author | Xuan Jiang Jun Wang Lin Gan Zengshuai Wu Tong Wu Fengyang Li Xiaowei Xu Liancheng Lei Na Li |
| author_facet | Xuan Jiang Jun Wang Lin Gan Zengshuai Wu Tong Wu Fengyang Li Xiaowei Xu Liancheng Lei Na Li |
| author_sort | Xuan Jiang |
| collection | DOAJ |
| description | Abstract As the incessant emergence of drug-resistant bacterial strains, bacterial pneumonia poses a serious threat to the public health worldwide. There is an urgent need to explore unconventional therapeutic strategies. Carbon dots are usually designed to directly kill bacteria, however, carbon dots that enhance the anti-infection function of immune cells are rarely reported. In the present study, CDots were synthesized with ascorbic acid and polyethyleneimine, exhibiting outstanding biocompatibility. Functionally, the CDots exhibited a well therapeutic impact on bacterial pneumonia induced by gram-positive multidrug-resistant Staphylococcus aureus (MRSA) or gram-negative Klebsiella pneumoniae (K. pneumoniae) in mice. Utilizing in vitro models of macrophages infected with MRSA and K. pneumoniae, we discovered that CDots augmented the M1 polarization of macrophages, subsequently enhancing their survival and activity of phagocytosis and bactericidal. Further investigations through molecular dynamics simulations and in vitro experiments validated that CDots directly bind to the catalytic subunit (PIK3CD) of phosphoinositide 3-kinase (PI3K), resulting in the inhibition of the PI3K/AKT/mTOR signaling pathway. Moreover, the crucial domain for the binding was located in amino acids 752–787 of PIK3CD. In summary, CDots exerted a protective effect on bacterial pneumonia by targeting the PIK3CD and fostering the PI3K-mediated M1 polarization of macrophages. These findings not only reveal a new role of CDots in the treatment of bacterial pneumonia, but also provide potential targets for future treatment strategies. Graphical Abstract |
| format | Article |
| id | doaj-art-1e6c443451e546bebaadcaf868bb481a |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-1e6c443451e546bebaadcaf868bb481a2025-08-20T02:19:57ZengBMCJournal of Nanobiotechnology1477-31552025-04-0123111610.1186/s12951-025-03399-7Carbon dot-based treatment for bacterial pneumonia by promoting a PI3K-mediated M1 polarization of macrophagesXuan Jiang0Jun Wang1Lin Gan2Zengshuai Wu3Tong Wu4Fengyang Li5Xiaowei Xu6Liancheng Lei7Na Li8State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityJilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityState Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityAbstract As the incessant emergence of drug-resistant bacterial strains, bacterial pneumonia poses a serious threat to the public health worldwide. There is an urgent need to explore unconventional therapeutic strategies. Carbon dots are usually designed to directly kill bacteria, however, carbon dots that enhance the anti-infection function of immune cells are rarely reported. In the present study, CDots were synthesized with ascorbic acid and polyethyleneimine, exhibiting outstanding biocompatibility. Functionally, the CDots exhibited a well therapeutic impact on bacterial pneumonia induced by gram-positive multidrug-resistant Staphylococcus aureus (MRSA) or gram-negative Klebsiella pneumoniae (K. pneumoniae) in mice. Utilizing in vitro models of macrophages infected with MRSA and K. pneumoniae, we discovered that CDots augmented the M1 polarization of macrophages, subsequently enhancing their survival and activity of phagocytosis and bactericidal. Further investigations through molecular dynamics simulations and in vitro experiments validated that CDots directly bind to the catalytic subunit (PIK3CD) of phosphoinositide 3-kinase (PI3K), resulting in the inhibition of the PI3K/AKT/mTOR signaling pathway. Moreover, the crucial domain for the binding was located in amino acids 752–787 of PIK3CD. In summary, CDots exerted a protective effect on bacterial pneumonia by targeting the PIK3CD and fostering the PI3K-mediated M1 polarization of macrophages. These findings not only reveal a new role of CDots in the treatment of bacterial pneumonia, but also provide potential targets for future treatment strategies. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03399-7Carbon DotsMultidrug-resistantBacterial pneumoniaPIK3CDMacrophage polarization |
| spellingShingle | Xuan Jiang Jun Wang Lin Gan Zengshuai Wu Tong Wu Fengyang Li Xiaowei Xu Liancheng Lei Na Li Carbon dot-based treatment for bacterial pneumonia by promoting a PI3K-mediated M1 polarization of macrophages Journal of Nanobiotechnology Carbon Dots Multidrug-resistant Bacterial pneumonia PIK3CD Macrophage polarization |
| title | Carbon dot-based treatment for bacterial pneumonia by promoting a PI3K-mediated M1 polarization of macrophages |
| title_full | Carbon dot-based treatment for bacterial pneumonia by promoting a PI3K-mediated M1 polarization of macrophages |
| title_fullStr | Carbon dot-based treatment for bacterial pneumonia by promoting a PI3K-mediated M1 polarization of macrophages |
| title_full_unstemmed | Carbon dot-based treatment for bacterial pneumonia by promoting a PI3K-mediated M1 polarization of macrophages |
| title_short | Carbon dot-based treatment for bacterial pneumonia by promoting a PI3K-mediated M1 polarization of macrophages |
| title_sort | carbon dot based treatment for bacterial pneumonia by promoting a pi3k mediated m1 polarization of macrophages |
| topic | Carbon Dots Multidrug-resistant Bacterial pneumonia PIK3CD Macrophage polarization |
| url | https://doi.org/10.1186/s12951-025-03399-7 |
| work_keys_str_mv | AT xuanjiang carbondotbasedtreatmentforbacterialpneumoniabypromotingapi3kmediatedm1polarizationofmacrophages AT junwang carbondotbasedtreatmentforbacterialpneumoniabypromotingapi3kmediatedm1polarizationofmacrophages AT lingan carbondotbasedtreatmentforbacterialpneumoniabypromotingapi3kmediatedm1polarizationofmacrophages AT zengshuaiwu carbondotbasedtreatmentforbacterialpneumoniabypromotingapi3kmediatedm1polarizationofmacrophages AT tongwu carbondotbasedtreatmentforbacterialpneumoniabypromotingapi3kmediatedm1polarizationofmacrophages AT fengyangli carbondotbasedtreatmentforbacterialpneumoniabypromotingapi3kmediatedm1polarizationofmacrophages AT xiaoweixu carbondotbasedtreatmentforbacterialpneumoniabypromotingapi3kmediatedm1polarizationofmacrophages AT lianchenglei carbondotbasedtreatmentforbacterialpneumoniabypromotingapi3kmediatedm1polarizationofmacrophages AT nali carbondotbasedtreatmentforbacterialpneumoniabypromotingapi3kmediatedm1polarizationofmacrophages |