Abstract
Early noninvasive screening and regression therapy for vulnerable atherosclerotic plaques remain challenging. In this study, it is aimed to develop a new approach for the active targeting of atherosclerotic plaques with nano-agents to aid imaging and treatment. Biocompatible hyaluronic acid (HA)-guided cerasomes are generated to selectively target CD44-positive cells within the plaque in in vitro studies and in vivo testing in Apoe-/- mice. Rosuvastatin (RST) is encapsulated in the HA-guided cerasome nano-formulation to produce HA-CC-RST, which results in significant plaque regression as compared to treatment with the free drug. Moreover, gadodiamide-loaded HA-CC enhances magnetic resonance images of vulnerable plaques, thereby attaining the goal of improved simultaneous treatment and imaging. Transcriptomic analysis confirms plaque regression with HA-CC-RST treatment, which potentially benefits from the anti-inflammatory effect of RST. In summary, a safe and efficient nano-formulation for the targeted delivery of active agents to atherosclerotic plaques is developed and may be applicable to other diagnostic and therapeutic agents for atherosclerosis treatment.
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