Macrophage membrane-biomimetic nanovehicles delivering amygdalin halt pyroptosis propagation and alleviate endometriosis-associated neuropathic pain.

The clinical management of endometriosis encounters a significant obstacle: existing therapies inadequately address both the inhibition of ectopic lesion proliferation and the mitigation of the neuroinflammation associated with chronic pain. To tackle this dual challenge, this research created a bioinspired dual-targeted nanotherapeutic platform called Amy@NPs-MM/PL1. The platform is made up of biodegradable polymeric nanoparticles that are filled with amygdalin, hidden by macrophage membranes to avoid the immune system and target inflammatory sites, and linked to PL1 peptides to actively recognize lesion stromal cells. Characterization of the material showed that it had good nanoscale properties and was stable. Mechanistically, the platform effectively inhibits the pyroptosis process in endometrial stromal cells, thereby blocking the generation and pyroptosis propagation to neurons at the source. Animal studies showed that Amy@NPs-MM/PL1 greatly lowers the number of lesions, eases pain sensitivity and depressive-like behaviors, and lessens neuroinflammation. Additional metabolomic analysis indicated that the treatment reinstates metabolic homeostasis systemically. The developed nanoplatform facilitates synchronized intervention in both localized lesion pathology and central nervous system sensitization, presenting an innovative material-based approach for the comprehensive treatment of endometriosis.