Breaking Iron Homeostasis: Iron Capturing Nanocomposites for Combating Bacterial Biofilm
Wenyue Sun
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, 130012 China
These authors contribute equally to this work.
Search for more papers by this authorJiao Sun
Department of Cell Biology, Norman Bethune College of Medicine, Jilin University, Changchun, 130021 China
These authors contribute equally to this work.
Search for more papers by this authorQihang Ding
Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea
These authors contribute equally to this work.
Search for more papers by this authorManlin Qi
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorJing Zhou
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorYujia Shi
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorJia Liu
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorMiae Won
Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea
TheranoChem Incorporation, Seoul, 02856, Republic of Korea
Search for more papers by this authorProf. Xiaolin Sun
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorProf. Xue Bai
State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, 130012 China
Search for more papers by this authorCorresponding Author
Prof. Biao Dong
State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, 130012 China
Search for more papers by this authorCorresponding Author
Prof. Jong Seung Kim
Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea
TheranoChem Incorporation, Seoul, 02856, Republic of Korea
Search for more papers by this authorCorresponding Author
Prof. Lin Wang
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorWenyue Sun
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, 130012 China
These authors contribute equally to this work.
Search for more papers by this authorJiao Sun
Department of Cell Biology, Norman Bethune College of Medicine, Jilin University, Changchun, 130021 China
These authors contribute equally to this work.
Search for more papers by this authorQihang Ding
Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea
These authors contribute equally to this work.
Search for more papers by this authorManlin Qi
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorJing Zhou
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorYujia Shi
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorJia Liu
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorMiae Won
Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea
TheranoChem Incorporation, Seoul, 02856, Republic of Korea
Search for more papers by this authorProf. Xiaolin Sun
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorProf. Xue Bai
State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, 130012 China
Search for more papers by this authorCorresponding Author
Prof. Biao Dong
State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun, 130012 China
Search for more papers by this authorCorresponding Author
Prof. Jong Seung Kim
Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea
TheranoChem Incorporation, Seoul, 02856, Republic of Korea
Search for more papers by this authorCorresponding Author
Prof. Lin Wang
Department of Oral Implantology, Jilin Provincial Key Laboratory of Sciences and Technology for Stomatology Nanoengineering, School and Hospital of Stomatology, Jilin University, Changchun, 130021 China
Search for more papers by this authorGraphical Abstract
Bacteria spend years in a dormant, inactive state, yet revive in some nutrient environments. Iron nutritional immunity strategy was proposed to target iron nutrients. We developed a nanoplatform that can deceive bacteria to uptake “fake iron” and concurrently extract iron ions from the surrounding bacteria milieu, starving pathogens to death.
Abstract
Given the scarcity of novel antibiotics, the eradication of bacterial biofilm infections poses formidable challenges. Upon bacterial infection, the host restricts Fe ions, which are crucial for bacterial growth and maintenance. Having coevolved with the host, bacteria developed adaptive pathways like the hemin-uptake system to avoid iron deficiency. Inspired by this, we propose a novel strategy, termed iron nutritional immunity therapy (INIT), utilizing Ga-CT@P nanocomposites constructed with gallium, copper-doped tetrakis (4-carboxyphenyl) porphyrin (TCPP) metal–organic framework, and polyamine-amine polymer dots, to target bacterial iron intakes and starve them. Owing to the similarity between iron/hemin and gallium/TCPP, gallium-incorporated porphyrin potentially deceives bacteria into uptaking gallium ions and concurrently extracts iron ions from the surrounding bacteria milieu through the porphyrin ring. This strategy orchestrates a “give and take” approach for Ga3+/Fe3+ exchange. Simultaneously, polymer dots can impede bacterial iron metabolism and serve as real-time fluorescent iron-sensing probes to continuously monitor dynamic iron restriction status. INIT based on Ga-CT@P nanocomposites induced long-term iron starvation, which affected iron-sulfur cluster biogenesis and carbohydrate metabolism, ultimately facilitating biofilm eradication and tissue regeneration. Therefore, this study presents an innovative antibacterial strategy from a nutritional perspective that sheds light on refractory bacterial infection treatment and its future clinical application.
Conflict of interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
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