Abstract

Ischemic stroke (IS) presents a formidable clinical challenge due to its complex pathophysiology, encompassing neuroinflammation and oxidative stress, alongside the lack of comprehensive diagnostic and therapeutic strategies. To address this, we designed a plant-based theranostic nanoplatform by coating apple exosome-like nanoparticles (ELNs) with polydopamine (PDA) and chelating gadolinium ions (Gd), denoted as PDA@ELNs/Gd. This platform exhibits enhanced penetration of the blood-brain barrier (BBB) and targeted accumulation in ischemic brain regions. The PDA coating serves as both a substrate for Gd chelation, enabling robust T1-weighted magnetic resonance imaging (MRI) contrast for non-invasive lesion detection, and a synergistic partner with the bioactive components of apple ELNs to provide dual-pathway neuroprotection. In vitro studies demonstrated that PDA@ELNs/Gd effectively scavenges reactive oxygen species, reprograms microglia from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype, and inhibits activation of the NF-κB/NLRP3 pathway. In a photothrombotic stroke (PT) mouse model, PDA@ELNs/Gd selectively accumulated in the ischemic hemisphere, provided clear MRI contrast, alleviated cerebral infarction injury, and significantly enhanced neurobehavioral recovery by protecting the ischemic penumbra. Transcriptomic analysis further revealed that PDA@ELNs/Gd extensively regulated pathways associated with neuroinflammation, extracellular matrix remodeling, and cell survival. Comprehensive biosafety studies affirmed minimal systemic toxicity. This work establishes a biocompatible, plant-derived theranostic platform that integrates MRI-guided diagnostics with multimodal therapy, representing a promising advancement in precise IS treatment.