Amino acid functionalization of Au-Ag@PDA with transferrin coupling for neuroprotection in mice with intracerebral hemorrhage.

Currently, the secondary injury mechanisms during the clinical management of intracerebral hemorrhage (ICH) at deep sites include iron-induced neurotoxicity and oxidative stress, leading to sustained neuronal damage and long-term neurological deficits. Therefore, we developed a multifunctional nanoplatform by coating branched and multi-spiky Au-Ag NPs with a polydopamine (PDA) layer, and further modifying them with D-Ser and L-Glu and functionalizing them with transferrin (Tf-GSAAP), exhibiting a good photothermal response in the second near-infrared window (NIR-II). The results of an in vivo test showed that the Tf-GSAAP NPs could effectively target the ICH site, where NIR-II photothermal therapy promoted neuronal survival; furthermore, the released D-Ser and L-Glu acted as co-agonists for the NMDA receptor, leading to significant neuroprotective and reparative effects. A mechanism for the neuroprotection and neurological function recovery after ICH mediated by Tf-GSAAP NPs through a NIR-II response was proposed, with higher expression of BDNF and NGF factors, and better ROS clearance. This study provides a proof-of-concept strategy of NIR-II photothermal therapy combined with neuromodulation to promote neurological recovery of deep tissue, offering a promising new direction for the treatment of ICH.