Researchers in China have developed a hybrid nanomaterial that captures and chemically degrades lipopolysaccharide (LPS), the potent bacterial endotoxin responsible for the catastrophic immune overreaction in sepsis, using a two-step mechanism that mimics how plants recognize bacterial invaders.
The “nano-chimeras,” described in Nature Communications on June 21, combine plant-derived nanovesicles displaying an LPS-binding protein with cerium-based nanozymes that hydrolyze the toxic portion of the molecule. In animal models, the approach effectively attenuated both local and systemic inflammation.
The endotoxin problem
LPS, also called endotoxin, is the major component of the outer membrane of Gram-negative bacteria. It consists of three structural regions: the toxic lipid A domain, a core oligosaccharide, and a long O-antigen polysaccharide chain. Lipid A is the business end, it binds to the TLR4-MD2 receptor complex on immune cells, triggering a cascade of cytokines that can spiral into septic shock, organ failure, and death.
The molecule is notoriously difficult to neutralize in the bloodstream. It is potent at nanomolar concentrations, meaning vanishingly small amounts can trigger severe inflammation. Competing biomolecules in blood serum make it hard for binding agents to reach LPS. And its lipid A moiety is chemically stable, conventional approaches can bind LPS but struggle to degrade it.
Existing treatments, including polymyxin B-based hemoperfusion and anti-LPS antibodies, suffer from toxicity, limited specificity in complex biological fluids, or an inability to actually destroy the molecule, they sequester it without inactivating it.
Capture and destroy
The new approach, developed by Lulu Jin, Chenyin Zhang, and colleagues at Zhejiang Provincial People’s Hospital, Zhejiang University, and the First Affiliated Hospital of Zhejiang Chinese Medical University, takes a fundamentally different tack.
The nano-chimeras, named Atv@Ce, fuse two functional components:
Step 1, Capture: Nanovesicles derived from Arabidopsis (a Brassicaceae plant) naturally display LORE (lipooligosaccharide-specific reduced elicitation) on their surface. LORE is a transmembrane protein that plants use to detect LPS, and it binds the molecule with high affinity, pulling it out of complex biological fluids even in the presence of competing proteins.
Step 2, Degrade: Cerium-based nanozymes integrated into the structure chemically hydrolyze the phosphate groups and glycosidic bonds in lipid A, breaking down the toxic core of the molecule. Unlike simple binding agents, this destroys the endotoxin itself.
The term “nano-chimera” reflects the fusion of two kingdoms, a biological recognition element borrowed from the plant immune system paired with a synthetic catalytic nanoparticle.
In vivo results
In animal models of both local and systemic inflammation, Atv@Ce effectively attenuated the inflammatory response. The plant-derived nanovesicles proved biocompatible, an advantage over synthetic delivery systems, which often face clearance by the immune system or toxicity concerns.
The authors describe the approach as “a biocompatible detoxification strategy with translational potential”, meaning the hybrid design could eventually be developed into a therapeutic for sepsis patients, for whom treatment options remain dangerously limited.
Sepsis affects approximately 49 million people worldwide each year, killing 11 million, according to the Global Burden of Disease study. Gram-negative bacteria account for a significant proportion of cases, and antibiotic resistance is making the problem worse, new approaches that directly neutralize bacterial toxins rather than just killing bacteria are urgently needed.
Caveats
The paper is published as an unedited manuscript preview, the final copy-edited version may differ. Specific quantitative data (binding affinities, cytokine reduction fold-changes, survival rates) are in the full text and supplementary materials but were not independently verified here.
The study employed an LPS-induced inflammation model; whether the approach works in a polymicrobial sepsis model (where live bacteria and multiple toxin types are present) is not addressed in the abstract. Atv@Ce targets only LPS from Gram-negative bacteria and would not address Gram-positive or fungal co-infections, which are common in clinical sepsis.
Long-term biodistribution and clearance of the cerium nanozymes in the body were not discussed in the available text, and manufacturing consistency of plant-derived nanovesicles at clinical scale remains an open question. Several other LPS-detoxifying nanozymes are in development, how Atv@Ce compares against them is not yet visible from the published data.
Source: Jin, L., Zhang, C., Yi, H. et al. “Lipopolysaccharide hydrolysis-targeting nano-chimeras detoxify endotoxin through specific adsorption and efficient degradation.” Nature Communications (2026). DOI: 10.1038/s41467-026-74689-3