Ligand-Modified Gold Nanoparticles as Mitochondrial Modulators: Regulation of Intestinal Barrier and Therapy for Constipation

Abstract

Intestinal metabolism-related diseases, such as constipation, inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, could be associated with the dysfunction of intestinal mitochondria. The mitochondria of intestinal epithelial cells are of great significance for promoting intestinal motility and maintaining intestinal metabolism. It is necessary for the prophylaxis and therapy of intestinal metabolism-related diseases to improve mitochondrial function. We investigated the effect of 4,6-diamino-2-pyrimidinethiol-modified gold nanoparticles (D-Au NPs) on intestinal mitochondria and studied the regulatory role of D-Au NPs on mitochondria metabolism-related disease. D-Au NPs improved the antioxidation capability of mitochondria, regulated the mitochondrial metabolism, and maintained intestinal cellular homeostasis via the activation of AMPK and regulation of PGC-1α with its downstream signaling (UCP2 and DRP1), enhancing the intestinal mechanical barrier. D-Au NPs improved the intestinal mitochondrial function to intervene in the emergence of constipation, which could help develop drugs to treat and prevent mitochondrial metabolism-related diseases. Our findings provided an in-depth understanding of the mitochondrial effects of Au NPs for improving human intestinal barriers.

Revitalizing Ancient Mitochondria with Nano‐Strategies: Mitochondria‐Remedying Nanodrugs Concentrate on Disease Control

“…Reproduced with permission. [ 371 ] Copyright 2023, American Chemical Society. F) Schematic illustration of HA‐CYS‐SA, HCS.…”

“…discovered that 4,6‐diamino‐2‐pyrimidinethiol‐coated gold NPs (D‐Au NPs) could repair the intestinal barrier and alleviate constipation through various mitochondrial protection mechanisms (Figure 22D). [ 371 ] D‐Au NPs demonstrated a remarkable enhancement in the antioxidation capability of mitochondria, effectively modulated mitochondrial metabolism, and ensured the overall stability of intestinal cells by activating AMPK and regulating PGC‐1α, along with its downstream signaling molecules (uncoupling protein 2 (UCP2) and DRP1), within IECs. These effects significantly improved the integrity of the intestinal mechanical barrier.…”

Nanocrystalline Cellulose Modulates Dysregulated Intestinal Barriers in Ulcerative Colitis

“…UC is caused by the impairment of the intestinal barriers, , which is mainly manifested in the disturbance of gut microbiota, − the decrease of intestinal mucus, and the damage of epithelial tight junctions. − As the intestinal biological barrier, gut microbiota can affect the health of the body. − Gut microbiota can provide nutrients, regulate metabolism, modulate intestinal homeostasis, and maintain the immune function of the body. − As the intestinal chemical barrier, intestinal mucus can maintain intestinal homeostasis, protect the gut from mechanical, chemical, and biological attacks, protect intestinal cells from external toxins, digestive enzymes, and bacteria, protect epithelial cells from dehydration and mechanical stress, and be as a surface cleaner . As the intestinal mechanical barrier, intestinal epithelial cells are arranged tightly to form the “gut wall” relying on the intercellular and intracellular tight junction proteins (such as ZO-1 and occludin). − The intestinal barriers could prevent toxins, bacteria, viruses, and other harmful substances, while allowing beneficial substances to pass through …”