A Self-Sustaining Near-Infrared Afterglow Chemiluminophore for High-Contrast Activatable Imaging.

Afterglow imaging holds great promise for ultrasensitive bioimaging due to its elimination of autofluorescence. Self-sustaining afterglow molecules (SAMs), which enable all-in-one photon sensitization, chemical defect formation and afterglow generation, possess a simplified, reproducible, and efficient superiority over commonly used multi-component systems. However, there is a lack of SAMs, particularly those with much brighter near-infrared (NIR) emission and structural flexibility for building high-contrast activatable imaging probes. To address these issues, this study for the first time reports a methylene blue derivative-based self-sustaining afterglow agent (SAN-M) with brighter NIR afterglow chemiluminescence peaking at 710 nm. By leveraging the structural flexibility and tunability, an activatable nanoprobe (SAN-MO) is customized for simultaneously activatable fluoro-photoacoustic and afterglow imaging of peroxynitrite (ONOO- ), notably with a superior activation ratio of 4523 in the afterglow mode, which is at least an order of magnitude higher than other reported activatable afterglow systems. By virtue of the elimination of autofluorescence and ultrahigh activation contrast, SAN-MO enables early monitoring of the LPS-induced acute inflammatory response within 30 min upon LPS stimulation and precise image-guided resection of tiny metastatic tumors, which is unattainable for fluorescence imaging.

Cathepsin K-Activated Probe for Fluoro-Photoacoustic Imaging of Early Osteolytic Metastasis.

Precise detection of early osteolytic metastases is crucial for their treatment but remains challenging in the clinic because of the limited sensitivity and specificity of traditional imaging techniques. Although fluorescence imaging offers attractive features for the diagnosis of osteolytic metastases, it is hampered by limited penetration depth. To address this issue, a fluoro-photoacoustic dual-modality imaging probe comprising a near-infrared dye caged by a cathepsin K (CTSK)-cleavable peptide sequence on one side and functionalized with osteophilic alendronate through a polyethylene glycol linker on the other side is reported. Through systematic in vitro and in vivo experiments, it is demonstrated that in response to CTSK, the probe generated both near-infrared fluorescent and photoacoustic signals from bone metastatic regions, thus offering a potential strategy for detecting deep-seated early osteolytic metastases.