Construction of fibromodulin and borneol-clacked phosphorus dendrimer nanoparticles to reduce inflammation and oxidative stress in BBB to nursing care and ischemic stroke therapy.

The formulation of novel multi-target combination therapies to address ischemic stroke (ICS) continues to pose significant challenges. This work presents a proof-of-concept display of a proficient nanomedicine formulation consisting of macrophage membrane (MM)-camouflaged phosphorous dendrimer (designated as PD)/fibromodulin (FB) nanoparticles (NPs) clacked with the antioxidant borneol (BN) to regulate both microglia and neurons for efficient ICS therapy. The developed MM@PD-FB/BN NPs, averaging 260 nm in size, exhibit excellent colloidal stability, prolonged BN release kinetics, and favorable cytocompatibility. Due to MM decoration, the MM@PD-FB/BN NPs can traverse the blood-brain barrier, influence microglia to produce anti-inflammatory (PD and FB) and antioxidative (FB and BN) effects in vitro, facilitating oxidative stress mitigation, microglia M2 polarization, and decreased proinflammatory cytokine secretion, while also acting on neuronal cells to exhibit anti-apoptotic properties. In a middle cerebral artery occlusion (MCAO) model, engineered MM@PD-FB/BN NPs demonstrate improved antioxidant, anti-inflammatory, and anti-apoptotic therapeutic effects, modulating the brain microenvironment to restore blood flow. The engineered MM-coated NPs, comprising active components of phosphorous dendrimers, FB, and BN, capable of comprehensively modulating the brain's inflammatory milieu, may broaden the treatment and nursing care of ischemic stroke.