Near-Infrared II Fluorescence Imaging and Image-Guided siRNA Therapy of Atherosclerosis

Targeting
Ca2+/calmodulin-dependent protein kinase γ
(CaMKIIγ) in macrophages using RNAi nanotechnology represents
an innovative and promising strategy in the diagnosis and treatment
of atherosclerosis. Nevertheless, it remains elusive because of the
current challenges associated with the systemic delivery of siRNA
nanoparticle (NP) to atheromatous plaques and the complexity of atherosclerotic
plaques. Here, we demonstrate the potential of a thienothiadiazole-based
near-infrared-II (NIR-II) organic aggregation-induced emission (AIE)
platform encapsulated with the Camk2g siRNA to effectively target
CaMKIIγ in macrophages for dynamic imaging and image-guided
gene therapy of atherosclerosis. The nanoparticles effectively decreased
CaMKIIγ expression and increased the expression of the efferocytosis
receptor MerTK in plaque macrophages, leading to a reduction in the
necrotic core area of the lesion in an aortic plaque model. Our theranostic
approach highlights the substantial promise of near-infrared II (NIR-II)
AIEgens for imaging and image-guided therapy of atherosclerosis.