Systemically administered platelet-inspired nanoparticles to reduce inflammation surrounding intracortical microelectrodes

Intracortical microelectrodes (IMEs) are essential for neural signal acquisition in neuroscience and brain-machine interface (BMI) systems, aiding patients with neurological disorders, paralysis, and amputations. However, IMEs often fail to maintain robust signal quality over time, partly due to neuroinflammation caused by vascular damage during insertion. Platelet-inspired nanoparticles (PIN), which possess injury-targeting functions, mimic the adhesion and aggregation of active platelets through conjugated collagen-binding peptides (CBP), von Willebrand Factor-binding peptides (VBP), and fibrinogen-mimetic peptides (FMP). Systemically administered PINs can potentially enhance hemostasis and promote the resealing of IME insertion-induced leaky blood-brain barrier (BBB), thereby attenuating the influx of blood-derived proteins into the brain parenchyma that trigger neuroinflammation. This study explores the potential of PINs to mitigate neuroinflammation at implant sites. Male Sprague Dawley rats underwent craniotomies and IME implantations, followed by a single dose of Cy5 labeled PINs (2 mg/kg). Rats were sacrificed at intervals from 0 to 4 days post-implantation (DPI) for biodistribution analysis using an in vivo live imaging system (IVIS) and immunohistochemistry (IHC) to assess neuroinflammation, BBB permeability, and active platelet distribution. Another cohort of rats received weekly PINs, trehalose buffer (TH, diluent control), or control nanoparticles (CP, PEG-coated liposomes) for 4 weeks, with similar endpoint analyses. Results indicated that PIN concentrations were significantly elevated near IME interfaces acutely (0-4 DPI) and after 4 weeks of repeated dosing. At 3 DPI, peak intensities of active platelets (CD62P), activated microglia/macrophages (CD68), and PINs were observed. Immunoglobulin G (IgG) was upregulated during the first 24 h near implant sites but declined thereafter. At 4 weeks, the PINs group exhibited higher intensities of active platelets and PINs, and reduced CD68 and IgG levels compared to controls. PINs effectively targeted the IME-tissue interface, alongside endogenous activated platelets, resulting in reduced neuroinflammatory and BBB-leakage markers compared to the diluent-only-infused control group. Repeated dosing of PINs presents a promising approach for enhancing the quality of neural recordings in future studies.