Precisely Targeting Cardiac Remodeling Nanomachine for Restarting Healthy Heartbeat.

Atrial fibrillation (AF) is a common arrhythmia that can cause serious symptoms and affect the quality of life of patients. Therefore, the treatment of AF has always faced challenges in the medical field. Here, Zn@Mg@MSNs@PEG nanosphere-based nanomachines with a unique composite structure in which Zn and Mg are deposited on the surface of mesoporous silica nanoparticle (MSNs) nanospheres, followed by polyethylene glycol (PEG) modification, display excellent acid-responsive properties due to their unique ion sputtering structure. The nanomaterials show autonomous mobility in PBS with acid input, without the use of energetic toxic fuels. This active release of Zn²⁺/Mg²⁺/H₂ improves the intracellular Ca²⁺/Na⁺/K⁺/Cl^- ratio via nanomachines. The intracellular Ca²⁺/Na⁺/K⁺/Cl^- gradients are the key to AF electrophysiology. Electrophysiology amelioration combined with oxidative stress and inflammatory mediator inhibition is found to mediate AF following Zn@Mg@MSNs@PEG nanomachine invasion. The designed star arrow-separated nanomachine system, activated by acidic conditions to enhance mobility and enable the targeted release of Zn²⁺, Mg²⁺, and H₂, effectively inhibits cardiac remodeling associated with AF by precisely targeting both structural and electrical abnormalities, achieving therapeutic effects without causing additional damage.