Surface Geometry of Cargo-less Gold Nanoparticles Is a Driving Force for Selective Targeting of Activated Neutrophils to Reduce Thrombosis in Antiphospholipid Syndrome.

ABSTRACT: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arterial, venous, and microvascular thrombosis where activated neutrophils play a determinant role. However, neutrophils are challenging to target given their short lifespan in circulation and spontaneous activation. Screening of a small library of gold nanoparticles (AuNPs) led to the discovery of a formulation capable of targeting activated neutrophil attachment and has demonstrated that star-shaped, anti-PSGL-1-antibody-coated AuNPs (aPSGL-1-AuNPs) were more efficacious compared with other shapes of AuNPs. Our findings further revealed an exciting and safe targeting mode toward activated neutrophils in the APS mouse model induced by human-patient-derived antiphospholipid IgGs. Our studies demonstrate that targeting is dependent on the specific topographical features of the highly segregated PSGL-1 on the activated neutrophil surface for which a high affinity shape-driven nanomedicine can be designed and implemented. As such, star-shaped aPSGL-1-AuNPs serve as a promising nanoimmunotherapy for immunothrombosis associated with neutrophil adhesion in APS.

SUBMITTER: Di L 

PROVIDER: S-EPMC10636870 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature