A Dual-Function CD47-Targeting Nano-Drug Delivery System Used to Regulate Immune and Anti-Inflammatory Activities in the Treatment of Atherosclerosis

Abstract

Atherosclerosis is a primary contributor to cardiovascular disease. Current studies have highlighted the association between the immune system, particularly immune cells, and atherosclerosis, although treatment options and clinical trials remain scarce. Immunotherapy for cardiovascular disease is still in its infancy. Bruton's tyrosine kinase (BTK), widely expressed in various immune cells, represents a promising therapeutic target for atherosclerosis by modulating the anti-inflammatory function of immune cells. This study introduces a polydopamine-based nanocarrier system to deliver the BTK inhibitor, ibrutinib, to atherosclerotic plaques with an active targeting property via an anti-CD47 antibody. Leveraging polydopamine's pH-sensitive reversible disassembly, the system offers responsive, controlled release within the pathologic microenvironment. This allows precise and efficient ibrutinib delivery, concurrently inhibiting the activation of the NF-κB pathway in B cells and the NLRP3 inflammasome in macrophages within the plaques. This treatment also modulates both the immune cell microenvironment and inflammatory conditions in atherosclerotic lesions, thereby conveying promising therapeutic effects for atherosclerosis in vivo. This strategy also provides a novel option for atherosclerosis treatment.