19F MRI-guided Flexible Low-intensity Focused Ultrasound for Drug Delivery and Molecular Targeted Therapy

Abstract

Non-site-specific, time-release and inefficient tumor penetration remain the major obstacles to the clinical efficacy of anticancer drugs. Novel strategies are therefore urgently needed for developing stimuli-responsive, local drug delivery systems that can increase drug penetration and accumulation at tumor sites. Here, we firstly describe an on-demand drug delivery system, AZD9291-PFCE nanoparticles (NPs) with 19F magnetic resonance imaging (19F MRI)-guided flexible low-intensity focused ultrasound (LIFU). Optimized AZD9291-PFCE NPs (size 73.9 ± 1.9 nm) reach high accumulation in non–small cell lung cancer (NSCLC) tumor tissue. Further, LIFU triggered drug release from AZD9291-PFCE NPs and specifically increased tumor vascular and tumor tissue permeability. Quantitative 19F MRI was used to measure NPs accumulation in tumors in real-time after LIFU irradiation and to monitor therapeutic efficacy. Thus, we present an innovative strategy to achieve on-demand release of AZD9291 and improve NSCLC EGFR-targeted therapy efficacy by integrating theranostic NPs and 19F MRI-guided LIFU.