Folate-guided AIE nanoparticles integrate macrophage-targeted fluorescence imaging and photodynamic immunomodulation in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and macrophage-driven immune dysregulation. Here, we developed a multifunctional nanoplatform (FA@4BC NPs) by encapsulating an AIE-active curcumin-derived photosensitizer (4BC) within folate-functionalized PEGylated liposomes. The system enables precise targeting of activated macrophages through folate receptor-β (FR-β) recognition, and upon laser irradiation, efficiently generates singlet oxygen (1O2), promoting M1-to-M2 macrophage polarization and initiating anti-inflammatory signaling pathways. In a collagen-induced arthritis (CIA) mouse model, FA@4BC NPs selectively accumulated in inflamed joints, enabling high-contrast in vivo fluorescence imaging. Histological and immunohistochemical analyses further demonstrated that this nanoplatform effectively improved synovial architecture, reduced inflammatory cell infiltration, and alleviated cartilage damage, exhibiting desirable anti-inflammatory and bone-protective effects. This study demonstrates a non-cytotoxic photodynamic therapy strategy based on natural product, integrating targeted imaging, immune modulation, and joint repair, offering a promising paradigm for precision RA therapy.