Low-intensity pulsed ultrasound responsive phase-change nanoparticles loaded with rapamycin for targeted therapy of atherosclerotic plaques

Atherosclerosis (AS), the primary cause of cardio-cerebrovascular diseases, is characterized by plaques that trigger acute ischemic events. Current therapies face challenges in targeted delivery and efficient local drug release, limiting precise diagnosis and treatment. To address this, we developed an ultrasound-responsive nanosystem for integrated AS diagnosis and therapy. The nanosystem, based on polylactic-co-glycolic acid (PLGA), encapsulates perfluoropentane (PFP) and rapamycin (RAP), and is surface-modified with PP1 peptide (PPP@RAP NPs). The NPs exhibited an average size of 162.63 nm and a drug loading capacity of 36.95%, demonstrating excellent targeting ability. Low-intensity pulsed ultrasound (LIPUS) induced the phase transition of PFP, enhancing ultrasound signals by 85.64% and enabling controlled drug release. In vivo studies showed a significant reduction in lesion lipid area by 25.99% (P < 0.001), highlighting the therapeutic efficacy of the nanosystem. This ultrasound-triggered, peptide-targeted strategy integrates imaging and therapy, offering a promising approach for precise AS intervention with significant clinical translational potential.