Endogenous Near-Infrared Chemiluminescence: Imaging-Guided Non-Invasive Thrombolysis and Anti-Inflammation Based on a Heteronuclear Transition Metal Complex.

Abstract

Conventional therapy to treat thrombi (blood clots) has significant limitations: i) inflammation; ii) bleeding side effects; iii) re-embolisation, and iv) in situ thrombi that are not visible. Here it is reported that Cu2Ir nanoparticles (NPs) with a Cu-coordinated tetraphenylporphyrin (TPP) core and cyclometalated Ir(C^N)₂(N^N) substituents integrate long-lived near-infrared (NIR) chemiluminescence (CL) imaging, photothermal therapy (PTT) and photodynamic therapy (PDT) for thrombolysis, with antioxidant and anti-inflammatory properties. Based on density functional theory calculations the chemiluminescent reaction site between TPP and peroxynitrite (ONOO^-) is confirmed for the first time. The presence of the transition metal significantly improves the chemiluminescent properties of TPP. Upon specific activation by ONOO^-, Cu2Ir NPs exhibited more than 30-fold NIR CL intensity than TPP NPs, and the luminescence lasted for 60 min allowing for precise and long-lasting dynamic tracking of thrombi. Cu2Ir NPs achieved non-invasive safe thrombolytic therapy triggered by NIR irradiation at the signaling site. 72.3% blood reperfusion is obtained for nearly complete restoration of blood flow, and re-embolism is prevented in a mouse carotid artery model. Furthermore, Cu2Ir NPs scavenged excess reactive oxygen/nitrogen species (RONS) and reduced inflammatory factors. Cu2Ir NPs hold promise as a single-molecule strategy for diagnosing and treating diseases associated with thrombosis.