Multifunctional carbonized nanogels to treat lethal acute hepatopancreatic necrosis disease

BackgroundShrimp aquaculture has suffered huge economic losses over the past decade due to the outbreak of acute hepatopancreatic necrosis disease (AHPND), which is mainly caused by the bacteriaVibrio parahaemolyticus(V. parahaemolyticus) with the virulence pVA1 plasmid, which encodes a secretory photorhabdus insect-related (Pir) toxin composed of PirA and PirB proteins. The Pir toxin mainly attacks the hepatopancreas, a major metabolic organ in shrimp, thereby causing necrosis and loss of function. The pandemic of antibiotic-resistant strains makes the impact worse.MethodsMild pyrolysis of a mixture of polysaccharide dextran 70 and the crosslinker 1,8-diaminooctane at 180 ℃ for 3 h to form carbonized nanogels (DAO/DEX-CNGs) through controlled cross-linking and carbonization. The multifunctional therapeutic CNGs inherit nanogel-like structures and functional groups from their precursor molecules.ResultsDAO/DEX-CNGs manifest broad-spectrum antibacterial activity againstVibrio parahaemolyticusresponsible for AHPND and even multiple drug-resistant strains. The polymer-like structures and functional groups on graphitic-carbon within the CNGs exhibit multiple treatment effects, including disruption of bacterial membranes, elevating bacterial oxidative stress, and neutralization of PirAB toxins. The inhibition ofVibrioin the midgut of infected shrimp, protection of hepatopancreas tissue from Pir toxin, and suppressing overstimulation of the immune system in severeV. parahaemolyticusinfection, revealing that CNGs can effectively guard shrimp fromVibrioinvasion. Moreover, shrimps fed with DAO/DEX-CNGs were carefully examined, such as the expression of the immune-related genes, hepatopancreas biopsy, and intestinal microbiota. Few adverse effects on shrimps were observed.ConclusionOur work proposes brand-new applications of multifunctional carbon-based nanomaterials as efficient anti-Vibrioagents in the aquatic industry that hold great potential as feed additives to reduce antibiotic overuse in aquaculture.Graphical Abstract