A Photoinduced Electron Transfer-Based Hypochlorite-Specific Fluorescent Probe for Selective Imaging of Proinflammatory M1 in a Rheumatoid Arthritis Model

Abstract

The differentiation of the distinct phenotypes of macrophages is essential for monitoring the stage of inflammatory diseases for accurate diagnosis and treatment. Recent studies revealed that the level of hypochlorite (OCl–) varies from activated M1 macrophages (killing pathogens) to M2 (resolution of inflammation) during inflammation. Thus, we developed a simple and efficient fluorescent probe for discriminating M1 from M0 and M2. Herein, fluorescent-based imaging is applied as an alternative to immunohistochemistry, which is challenging due to the tedious process and high cost. We developed a hypochlorite-specific probe PMS-T to differentiate M1 and M2, employing a metabolism-oriented live-cell distinction. This probe enables the detection of inflammatory rheumatoid arthritis in an ex vivo mouse model. Thus, it can be a potential chemical tool for monitoring inflammatory diseases, including rheumatoid arthritis, that may overcome the existing barriers of immunohistochemistry.

Chronological development of functional fluorophores for bio-imaging

“…Fluorescent probe performance must be thoroughly assessed, considering factors like toxicity, photo-bleaching, and in vivo bio-distribution, before being applied in clinical settings. By making progress in this 164 area, we will be better able to understand intelligent probe design, evaluate their efficacy, and ultimately gain profound insights into biological systems, which will improve illness detection and therapy. As technology continues to evolve, fluorescent imaging is expected to play an increasingly vital role in enhancing our understanding of biological processes, enabling earlier disease detection, guiding treatments, and providing valuable insights into cellular and molecular interactions.…”

“…Ex vivo fluorescence imaging of the back leg/paws from the rheumatoid arthritis-induced mice model. The illustrations were reproduced with permission from American Chemical Society, copyright 2023 164.…”

Emerging advances in fluorescence imaging and phototherapy of arthritis

“…Another S‐containing probe 11 undergoes enhanced FL intensity after oxidation by HClO. [ 161 ] Unlike phenothiazine and probe 11 , probe 9 undergoes FL quenching upon reaction with HClO, which makes it difficult to accurately reflect the degree of inflammation. The problem was solved when the internal standard down‐conversion nanoparticles (DCNP) (1550 nm) and 1,2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine–poly(ethylene glycol) (PEG) were assembled to form DCNP@ 9 @PEG (Figure 2B).…”

Small-molecule fluorescent probes for bioactive species in inflammatory disease: arthritis, pneumonia and hepatitis

“…13A) that specifi-cally detected hypochlorite (ClO − ) metabolites. 71 The probe used the rigid pentacyclic pyridine structure based on D-A-D with high fluorescence quantum yield as the fluorescence skeleton, introducing 4-(methylthio) benzaldehide as the oxidation site of ClO − at position 7, and N-(2-aminoethyl)-4-methylbenzene sulfonamide as the recognition group of organelle. With the increased of ClO − concentration, the sulfur atom in 4-(methylthio) benzaldehide was oxidized, and the photoinduced electron transfer (PET) response was triggered, thus causing the significant increase of fluorescence intensity at 500 nm.…”