Alleviating Neuroinflammation through Photothermal Conjugated Polymer Nanoparticles by Regulating Reactive Oxygen Species and Ca²⁺ Signaling

Neuroinflammation is one of the important manifestations of the amyloid β peptide (Aβ) protein-induced neurotoxic signaling pathway in which the aggregation of Aβ causes an increase in reactive oxygen species (ROS) and Ca2+ concentration. Here, near-infrared (NIR) photothermal-responsive conjugated polymer nanoparticles were designed to regulate ROS and Ca2+ signaling to alleviate neuroinflammation. Under 808 nm laser irradiation, the nanoparticles effectively penetrated the blood–brain barrier (BBB) and reduced the aggregation of Aβ and partially disaggregated the aggregates outside the cell, thereby reducing ROS content which downregulated the oxidative stress damage to cells. Meanwhile, the nanoparticles reduced the concentration of Ca2+ by inhibiting the transient receptor potential melastatin-related 2 (TRPM2) ion channel inside the cell. Ultimately, the concentration of inflammatory factor tumor necrosis factor-α was decreased. This study provides an effective strategy to reduce neuroinflammation by simultaneously regulating ROS and Ca2+ signaling.