Breaking Iron Homeostasis: Iron Capturing Nanocomposites for Combating Bacterial Biofilm

Wenyue Sun, Jiao Sun, Qihang Ding, Manlin Qi, Jing Zhou, Yujia Shi, Jia Liu, Miae Won, Xiaolin Sun, Xue Bai, Biao Dong, Jong Seung Kim, Lin Wang

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Article numbere202319690
JournalAngewandte Chemie - International Edition
Volume63
Issue number14
DOIs
Publication statusPublished - 2024 Apr 2

Bibliographical note

Publisher Copyright:
© 2024 Wiley-VCH GmbH.

Keywords

  • antibacterial therapy
  • gallium
  • Iron nutritional immunity therapy
  • photodynamic therapy
  • photothermal therapy

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry

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