Fluorescence imaging in the second nearinfrared (NIR-II) window holds great promise for in vivo visualization of amyloid-β (Aβ) pathology, which can facilitate characterization and deep understanding of Alzheimer's disease (AD); however, it has been rarely exploited. Herein, we report the development of NIR-II fluorescent reporters with a donor-π-acceptor (D-π-A) architecture for specific detection of Aβ plaques in AD-model mice. Among all the designed probes, DMP2 exhibits the highest affinity to Aβ fibrils and can specifically activate its NIR-II fluorescence after binding to Aβ fibrils via suppressed twisted intramolecular charge transfer (TICT) effect. With suitable lipophilicity for ideal blood-brain barrier (BBB) penetrability and deep-tissue penetration of NIR-II fluorescence, DMP2 possesses specific detection of Aβ plaques in in vivo AD-model mice. Thus, this study presents a potential agent for non-invasive imaging of Aβ plaques and deep deciphering of AD progression.

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.

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past few decades. [5] In particular, activatable probes that can be specifically turned on to emit fluorescence by various cancerous biomarkers have been developed, [6] leading to significant improvement in the precision of tumor resection. [7] For instance, Urano et al. have developed a γ-glutamyltranspeptidase-responsive fluorescent probe that can light up tiny ovarian cancer nodules within 10 min [5c] and Bogyo et al. have reported a dual proteasesactivated fluorescent probe with improved specificity and sensitivity in localizing lung cancer metastases of <1 mm in diameter. [8] In spite of these encouraging advances, fluorescence imaging always suffers from some inherent limitations including photo bleaching, shallow tissuepenetration-depth, and high background signal arising from the autofluorescence of biological tissues upon light excitation. In this context, developing new strategies for creating luminescent probes with improved specificity and accuracy in discriminating cancerous lesions from normal tissues during the surgery is fundamentally important. [9] Chemiluminescence has been regarded as an alternative choice of constructing sensitive probes for biosensing and imaging. [10] Unlike fluorescence, chemiluminescence utilizes chemical reactions rather than photoexcitation to trigger the luminescence. As a consequence, chemiluminescence imaging can remarkably suppress the interference of autofluorescence to give rise to higher signal-to-noise ratio and better sensitivity for tumor detection in comparison with conventional fluorescence imaging. [11] As an attempt, Ding et al. have reported a chemiluminescent dioxetane-based nanoparticle for image-guided cancer surgery, [12] but it is an "always-on" probe, which has poor specificity and high background compared to activatable probe, and thus is unfavorable for tumor detection during a surgical practice. In recent years, a series of activatable chemiluminescent probes based on Schaap's dioxetanes have been developed for selective detection and imaging of various biomarkers such as cathepsin B, nitroreductase, β-galactosidase, reactive species, granzyme B and aminopeptidases, both in vitro and in vivo. [13] However, existing activatable chemiluminescent probes have not been explored for image-guided tumor surgery.Aminopeptidase N/CD13 (APN), a transmembrane metalloprotease that can preferentially hydrolyze N-terminal alanine from polypeptides, is the most studied cancer-related aminopeptidase. [14] Plentiful studies have demonstrated that APN is Developing smart molecular probes for assisting surgeons to precisely detect cancerous tissues and to completely remove all of them during the surgery is urgently required. Conventional fluorescent probes allow for tumor detection but with limited signal-to-noise ratio. Herein, an aminopeptidase N/ CD13 (APN)-activated chemiluminescent probe (APN-ACLP) is reported for sensitive imaging and precise resection of malignant tumors. The APN-ACLP probe is based on acryl-substituted phenoxy-dioxetane that is coupled with...

Fluorescence imaging in the second nearinfrared (NIR-II) window holds great promise for in vivo visualization of amyloid-β (Aβ) pathology, which can facilitate characterization and deep understanding of Alzheimer's disease (AD); however, it has been rarely exploited. Herein, we report the development of NIR-II fluorescent reporters with a donor-π-acceptor (D-π-A) architecture for specific detection of Aβ plaques in AD-model mice. Among all the designed probes, DMP2 exhibits the highest affinity to Aβ fibrils and can specifically activate its NIR-II fluorescence after binding to Aβ fibrils via suppressed twisted intramolecular charge transfer (TICT) effect. With suitable lipophilicity for ideal blood-brain barrier (BBB) penetrability and deep-tissue penetration of NIR-II fluorescence, DMP2 possesses specific detection of Aβ plaques in in vivo AD-model mice. Thus, this study presents a potential agent for non-invasive imaging of Aβ plaques and deep deciphering of AD progression.