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Photoacoustic (PA) imaging shows promise in the sensitive detection of caspase‐3 activated in early tumor apoptosis in response to chemotherapy; smart PA probes are thus in high demand. Herein, we report the first smart PA probe (1‐RGD) responsive to caspase‐3, enabling real‐time and high‐resolution imaging of tumor apoptosis. 1‐RGD is designed to leverage the synergetic effect of active delivery and caspase‐3 activation. It is selectively recognized by active caspase‐3 to trigger peptide substrate cleavage and biocompatible macrocyclization‐mediated self‐assembly, leading to an amplified PA imaging signal and prolonged retention in apoptotic tumor cells. Strong, high‐resolution PA images are obtained in chemotherapy‐induced apoptotic tumors in living mice after intravenous administration with 1‐RGD, facilitating sensitive reporting of caspase‐3 activity and distribution within tumor tissues. Good vibrations: The caspase‐3‐mediated biocompatible macrocyclization and self‐assembly of a photoacoustic (PA) probe, 1‐RGD, into indocyanine green (ICG)‐containing nanoparticles is reported. The probe allows the enhancement of PA imaging signals for the real‐time detection of tumor apoptosis in living mice with high sensitivity and spatial resolution. [ABSTRACT FROM AUTHOR]

Drug Design: An 18F‐labeled caspase‐3‐sensitive nanoaggregation positron emission tomography tracer was prepared and evaluated for imaging the caspase‐3 activity in doxorubicin‐treated tumor xenografts. Enhanced retention of the 18F activity in apoptotic tumors is achieved through intramolecular macrocyclization and in situ aggregation upon caspase‐3 activation (see picture). [ABSTRACT FROM AUTHOR]

The caspase‐3 activity in doxorubicin‐treated tumor xenografts is studied by positron emission tomography (PET) using a novel 18F‐labeled caspase‐3‐sensitive nanoaggregation tracer. In their Communication on page 10511 ff., J. Rao, F. T. Chin, et al. show that the enzyme‐activatable tracer improves the PET imaging of apoptotic tumors by intramolecular macrocyclization and in situ aggregation of the cyclized tracer upon caspase‐3 activation. (Picture: Jim Strommer and Lydia‐Marie Joubert.) [ABSTRACT FROM AUTHOR]

Die Caspase ‐ 3 ‐ Aktivität in mit Doxorubicin behandelten Tumorxenotransplantaten wird unter Verwendung eines 18F ‐ markierten, für Caspase ‐ 3 empfindlichen Nanoaggregat ‐ bildenden Tracers mit Positronenemissionstomographie (PET) untersucht. In der Zuschrift auf S. 10705 ff. zeigen J. Rao, F. T. Chin et al., dass der Enzym ‐ aktivierbare Tracer durch intramolekulare Makrocyclisierung und In ‐ situ ‐ Aggregatbildung des cyclisierten Tracers nach Caspase ‐ 3 ‐ Aktivierung verfeinerte PET ‐ Bilder von apoptotischen Tumoren liefert. Bild: Jim Strommer und Lydia ‐ Marie Joubert. [ABSTRACT FROM AUTHOR]

Multimodal imaging probes have shown promise in both biomedical research and clinical diagnosis. However, the development of molecular probes capable of being switched on multimodality imaging signals in response to a biomarker of interest remains challenging. In this paper, we report a caspase-3-activatable small-molecule bimodal probe (Gd-IR780) for photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) of tumor apoptosis via caspase-3-triggered intramolecular macrocyclization and in situ self-assembly process. Upon interaction with caspase-3, Gd-IR780 can be efficiently converted into a macrocyclic product, Gd-IR780-MC , which subsequently self-assembles into near-infrared absorptive and paramagnetic nanoparticles (Gd-IR780-NPs), allowing to concurrently switch on PAI (∼4.3-fold at 855 nm) and MRI (r 1 relaxivity increases from 7.98 ± 0.03 mM−1 s−1 to 19.66 ± 0.7 mM−1 s−1 at 0.5 T) bimodal signals in caspase buffer. Noninvasive in vivo imaging results show that Gd-IR780 can enter apoptotic U87MG tumor tissues after systemic administration, and produce markedly enhanced PAI and MRI signals for high sensitivity and spatial-resolution visualization of caspase-3 activity in the doxorubicin-treated apoptotic U87MG tumor tissues. Gd-IR780 holds a good potential to report tumor apoptosis via combined PAI and MRI, which is beneficial for the early evaluation of antitumor efficacy in vivo. • First activatable photoacoustic (PA) and magnetic resonance (MR) bimodal probe for in vivo imaging of tumor apoptosis. • Caspase-3-mediated in situ self-assembly strategy was used to activate PA and MR bimodal signals simultaneously. • Enhanced PA and MR signals in DOX-treated tumors are achieved, beneficialfor the early monitoring of chemotherapy efficacy. [ABSTRACT FROM AUTHOR]