Long-alkyl-chain-modified near-infrared fluorescent probe for in vivo visualization of viscosity and ONOO- in inflammation.

Background

Rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) are prevalent immune diseases that pose substantial global public health burdens. Early, accurate molecular imaging of inflammatory biomarkers in situ remains a major challenge.

Results

Herein, we rationally designed a novel near-infrared (NIR) fluorescent probe, HCy-LD-mito, for high-contrast, crosstalk-free imaging of viscosity and ONOO- in mitochondria and LDs. Benefiting from the introduction of a long C12 alkyl chain, HCy-LD-mito exhibits an ultra-sensitive NIR fluorescence response to viscosity with a remarkable 530-fold signal enhancement, while displaying a highly rapid and specific response toward ONOO- at 560 nm. Taking advantage of this excellent performance, HCy-LD-mito successfully enabled precise spatial mapping of the dynamic changes of ONOO- and viscosity in LPS-induced zebrafish liver inflammation. In vivo experiments further demonstrated that HCy-LD-mito can specifically visualize inflammatory lesions in RA and IBD animal models with high signal-to-background ratio (SBR), and achieve timely, real-time evaluation of the therapeutic effects of methotrexate (MTX) for RA and 5-aminosalicylic acid (5-ASA) for IBD.

Significance

This work establishes a versatile molecular platform for precise inflammatory disease theragnostic and offers a rational design strategy for multi-organelle synergistic imaging probes.