Lipid Nanoparticles from Walp Mitigate Sepsis through Multimodal Protein Corona Formation.

Background: Plant-derived nanoparticles (PDNP) are nano-sized particles isolated from various edible plants that contain bioactive components involved in regulating cellular immune responses against pathogenic intrusion and inflammation.

Purpose: This study describes a novel PDNP derived from Walp (maca) that efficiently captures pro-inflammatory cytokines and acute phase proteins in its protein corona to enhance survival in two representative lethal models of sepsis.

Methods: Lipid nanoparticles were isolated from maca (MDNP) and triacylglycerols and phytoceramides were identified as major constituents using lipidomics. The physicochemical properties of MDNPs were determined, anti-inflammatory effects of MDNP were evaluated using models and using endotoxemia and cecal ligation and puncture (CLP) polymicrobial sepsis models. Proteomic analysis of MDNP in healthy or LPS-induced inflammatory plasma was used to determine the composition and inflammatory pathways modulated due to the MDNP protein corona.

Results: studies showed that MDNP were non-toxic, reduced macrophage activation, and effectively sequestered pro-inflammatory cytokines to mitigate NF- B activity under lipopolysaccharide (LPS) stimulation. In a pre-established LPS-induced endotoxemia model, MDNP-treated mice showed significantly reduced systemic pro-inflammatory cytokines and enhanced survival. Untargeted proteomics and pathway analysis of the MDNP protein corona identified an enrichment in acute phase proteins in MDNP-LPS plasma coronas. MDNP treatment also significantly improved survival in the CLP sepsis model in the absence of antibiotics.

Conclusion: This work identified MDNP as an efficient, plant-derived lipid NP that broadly sequesters and neutralizes a compilation of inflammatory mediators in their coronas, offering multimodal therapeutic potential for treating inflammatory diseases.