Gut microbiome-specific nanoparticle-based therapeutics for liver diseases

Table 1 Overview of different types of microbiome-inspired nanoparticles trialed in experimental liver disease

Type of nanoparticle	Animal model used	Details of treatments	Therapeutic outcomes	Microbiome-specific effects/ role in design	Ref.
pH/gut microbiota-responsive NC nanoparticles	High-fat diet-induced steatohepatitis in C57 mice	Nanoparticles containing NC 8 mg/kg/day, by gavage	Reduced weight gain, serum aspartate aminotransferase, alanine aminotransferase and lipid levels, improved liver and intestinal inflammation, and altered diversity of gut microbiota	Abundance of beneficial Bacteroidetes gradually increased, whereas that of Desulfobacterota and Proteobacteria decreased	[84]
Low-molecular weight chitosan-based selenium nanoparticles	High-fat diet-induced liver disease in C57 mice	Nanoparticles were gavaged orally at 200 mg/kg/day	Inhibited hepatic fat accumulation and markedly improved the intestinal barrier by increasing mucus secretion from goblet cells	Increased the abundance of mucus-associated microbiota (Bifido-bacterium,Akkermansia, and unclassified Muribaculaceae) and decreased the abundance of obesity-related bacteria (Anaerotruncus, Lachnoclostridium, and Proteus)	[88]
Macrophages modulating transcription factor XBP1s siRNA-loaded folic acid-modified TPGS nanoparticles	Fat-, fructose- and cholesterol-rich diet model in C57 mice	Injected intravenously (0.05 nmol/L, 100 μL) every 3 days for 4 weeks	Reduced weight gain, dyslipidemia, inflammatory cytokines extrahepatically, and ER stress, fat accumulation, and fibrosis in the liver	Higher relative abundance of Blautia and Bacteroides, and lower abundance of Actinobacteriota, Muribaculaceae and Bifidobacterium	[89]
Prebiotic-like silybin-2-hydroxypropyl-β-cyclodextrin inclusion nano-complex	High fat diet-fed hamsters	100 mg/kg/day silybin equivalent nanoparticles by oral gavage	Decreased hepatic lipid content, oxidative stress, and inflammation	Restored the gut microbiota, increased fecal excretion of bile acids and intestinal integrity	[92]
Hydrogen-based nanocapsule loaded with ammonia borane inside hollow mesoporous silica nanoparticles core	Diet- and genetic (db/db)-induced steatohepatitis in C57 mice	0.8 mg/day/mouse hydrogen in nanoparticles administered through diet	Reduced lipid synthesis and increased fatty acid catabolism	Increased the abundance of Akkermansia muciniphila	[95]
Lactobacillus plantarum ghosts based astaxanthin-loaded nanoparticles	Modified Lieber-DeCarli liquid diet (5% ethanol) in C57 mice	20 mg/kg/day nanoparticles by oral gavage	2.11 times higher plasma bioavailability, reduced oxidative stress	Biomimetic self-guided delivery	[97]
Nanoparticles based on exosome-like nanoparticles released by Lactobacillus rhamnosus GG	Lieber-DeCarli liquid diet (5% ethanol) in C57 mice	On last 3 days by daily gavage of 200 μL of nanoparticles (50 μg protein content)	Protected the intestine from ethanol-induced barrier dysfunction and the liver from steatosis and inflammation	Increase tight junction protein expression in intestinal epithelial cells	[98]
Exosome like nanoparticles derived from Phellinus linteus	Hepa 1-6 liver tumor cells in vitro and in vivo diethylnitrosamine (20 mg/kg) and 40 ppm N-nitrosomorpholine in drinking water for 24 weeks in ICR mice	10 mg/kg/orally protein containing nanoparticles in 200 μL, every 3 days for a total of 5 doses	Strong anti-proliferative, anti-migratory, and anti-invasive effects	Enhanced Lactobacillus, Turicibacter, and Enterorhabdus. Lactobacillus	[104]
Polyethylene glycol (CHO-PEG2000-CHO)-poly (ethyleneimine) (PEI25k)-citraconic anhydride-doxorubicin nanoparticles loaded with plasmid-encoded hsulf-1 enzyme	H22 hepatocarcinoma model	Nanoparticles containing doxorubicin 5 μg, hsulf-1 60 μg, in 200 μL/mouse, subcutaneous injection, for 5 days	Increased cytokine secretion and the intratumoral infiltration of CD4/CD8+ T cells with strong antitumor effects	Non-pathogenic Escherichia coli-based nanoparticles	[107]

NC: Nitidine chloride; XBP1s: X-box binding proteins 1; siRNA: Small interference RNA; TPGS: Tocopheryl polyethylene glycol succinate; ER: Endoplasmic reticulum; PEG: Polyethylene glycol; PEI: Polyethyleneimine; hsulf-1: Human sulfatase-1; ICR mice: Institute of Cancer Research mice.