Folate Receptor‐Targeted NIR‐II Dual‐Model Nanoprobes for Multiscale Visualization of Macrophages in Rheumatoid Arthritis

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation. Macrophages accelerate the pathological process of RA through the continuous cell accumulation and secretion of cytokines. Therefore, multiscale visualization of macrophages is of great significance for the early diagnosis of RA. In this work, folate receptor‐targeted Cptnc‐4F nanoprobes, named FA‐CF‐NPs, are developed for dual‐model molecular imaging of macrophages in RA mouse models. FA‐CF‐NPs exhibit complementary imaging advantages with high fluorescence sensitivity and resolution in the second near‐infrared window (NIR‐II) and promising photoacoustic (PA) imaging contrast with deep tissue penetration. The high affinity of the folate ligand on the surface of FA‐CF‐NPs to macrophages with overexpressed folate receptors ensures the specific targeting function of the nanoprobes for imaging in vivo. FA‐CF‐NPs are employed to achieve NIR‐II fluorescence imaging to accurately localize macrophages in the joint, obtaining a high signal‐to‐background ratio (SBR) of 15.5. Meanwhile, PA imaging is also performed to observe macrophage distribution in the longitudinal section of the whole joint. Moreover, macrophage infiltration is detected in the joint of RA mice with the absence of RA pathologies such as synovitis and cartilage loss. The results provide an opportunity for in vivo macrophage tracking and early diagnosis of RA.