Orally administrated liquid metal agents for inflammation-targeted alleviation of inflammatory bowel diseases

Sci Adv. 2024 Jul 12;10(28):eadn1745. doi: 10.1126/sciadv.adn1745. Epub 2024 Jul 12.

Abstract

Rapid drug clearance and off-target effects of therapeutic drugs can induce low bioavailability and systemic side effects and gravely restrict the therapeutic effects of inflammatory bowel diseases (IBDs). Here, we propose an amplifying targeting strategy based on orally administered gallium (Ga)-based liquid metal (LM) nano-agents to efficiently eliminate reactive oxygen and nitrogen species (RONS) and modulate the dysregulated microbiome for remission of IBDs. Taking advantage of the favorable adhesive activity and coordination ability of polyphenol structure, epigallocatechin gallate (EGCG) is applied to encapsulate LM to construct the formulations (LM-EGCG). After adhering to the inflamed tissue, EGCG not only eliminates RONS but also captures the dissociated Ga to form EGCG-Ga complexes for enhancive accumulation. The detained composites protect the intestinal barrier and modulate gut microbiota for restoring the disordered enteral microenvironment, thereby relieving IBDs. Unexpectedly, LM-EGCG markedly decreases the Escherichia_Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium, resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.

MeSH terms

  • Administration, Oral
  • Animals
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives
  • Catechin / chemistry
  • Catechin / pharmacology
  • Colitis / drug therapy
  • Disease Models, Animal
  • Gallium / chemistry
  • Gallium / pharmacology
  • Gastrointestinal Microbiome* / drug effects
  • Humans
  • Inflammation / drug therapy
  • Inflammatory Bowel Diseases* / drug therapy
  • Mice
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Catechin
  • epigallocatechin gallate
  • Gallium
  • Reactive Oxygen Species
  • Reactive Nitrogen Species