Biohybrid Fused-Cell Carrier for Programmable Therapeutic Modulation of Atherosclerosis.

Abstract

Cardiovascular disease, driven primarily by atherosclerosis, remains a leading cause of global mortality. Lipid-lowering therapies reduce risk by less than one-third, leaving substantial residual inflammation compounded by rapid drug clearance and limited plaque targeting. Biomimetic systems such as cell-membrane coating enhance lesion targeting but lack intrinsic activity and are prone to biological barriers. Herein, we engineered living fused cell (FC) microrobots combining mesenchymal stem cells and M2 macrophages, capable of inheriting the therapeutic ability of both and modulating pathophysiological responses. Gold nanowaxberries (AuMWs) conjugated to antisense miRNA33 were loaded into the FCs. In vivo AuMW-anti-miR33@FCs modulated inflammation and immune microenvironment, augmented cholesterol efflux, and reduced plaque burden by 64.9% versus controls. Treatment was tracked by photoacoustic imaging via AuMWs. Overall, this synergistic strategy offers a promising platform for atherosclerosis cardiovascular disease diagnosis and therapy.