Afterglow luminescent probes with high signal-to-background ratio show promise for in vivo imaging; however, such probes that can be selectively delivered into target sites and switch on afterglow luminescence remain limited. We optimize an organic electrochromic material and integrate it into near-infrared (NIR) photosensitizer (silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) and (poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene]) containing nanoparticles, developing an H 2 S-activatable NIR afterglow probe (F1 2+-ANP). F1 2+-ANP displays a fast reaction rate (1563 ± 141 M −1 s −1) and large afterglow turn-on ratio (~122-fold) toward H 2 S, enabling high-sensitivity and-specificity measurement of H 2 S concentration in bloods from healthy persons, hepatic or colorectal cancer patients. We further construct a hepatic-tumor-targeting and H 2 Sactivatable afterglow probe (F1 2+-ANP-Gal) for noninvasive, real-time imaging of tiny subcutaneous HepG2 tumors (<3 mm in diameter) and orthotopic liver tumors in mice. Strikingly, F1 2+-ANP-Gal accurately delineates tumor margins in excised hepatic cancer specimens, which may facilitate intraoperative guidance of hepatic cancer surgery.

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Tumor response to radiotherapy or ferroptosis is closely related to hydroxyl radical (•OH) production. Noninvasive imaging of •OH fluctuation in tumors can allow early monitoring of response to therapy, but is challenging. Here, we report the optimization of a diene electrochromic material (1-Br-Et) as a •OH-responsive chromophore, and use it to develop a near-infrared ratiometric fluorescent and photoacoustic (FL/PA) bimodal probe for in vivo imaging of •OH. The probe displays a large FL ratio between 780 and 1113 nm (FL780/FL1113), but a small PA ratio between 755 and 905 nm (PA755/PA905). Oxidation of 1-Br-Et by •OH decreases the FL780/FL1113 while concurrently increasing the PA755/PA905, allowing the reliable monitoring of •OH production in tumors undergoing erastin-induced ferroptosis or radiotherapy.

Enzyme‐activatable ratiometric near‐infrared (NIR) fluorescent probes enabling noninvasive imaging of enzyme activity in vivo are promising for biomedical research; however, such probes with ratiometric fluorescence emissions both in NIR window under a single NIR light excitation are largely unexplored. Here, a quenched NIR fluorophore of Cy5.5 is integrated with NIR fluorescent poly[2,6‐(4,4‐bis‐(2‐ethylhexyl)‐4H‐cyclopenta[2,1‐b;3,4‐b′]dithiophene)‐alt‐4,7(2,1,3‐benzothiadiazole)] (PCPDTBT)‐based semiconducting polymer nanoparticles (SPNs), and an αvβ3 integrin‐targeting and matrix metalloproteinase‐2 (MMP‐2)‐activatable ratiometric fluorescent probe (SPN‐MMP‐RGD) is developed. Under excitation at 660 nm, SPN‐MMP‐RGD shows “always‐on” fluorescence of PCPDTBT (830 nm) and activatable fluorescence of Cy5.5 (690 nm) toward MMP‐2, affording a remarkable ≈176‐fold enhancement in fluorescence intensity ratio between 690 and 830 nm (I690/I830) for sensitive detection of MMP‐2 activity in vitro and in tumor cells. By virtue of ratiometric fluorescence imaging independently of probe's concentration, SPN‐MMP‐RGD can not only accurately report on MMP‐2 levels regarding different tumor sizes, but also noninvasively delineate MMP‐2‐positive tiny gastric tumors metastasis in vivo. The authors’ study reveals the potential of SPN‐MMP‐RGD for ratiometric fluorescence imaging of MMP‐2 activity via combining two independent NIR fluorophores, which can be amenable for the design of other enzyme‐activatable ratiometric NIR fluorescent probes for reliable in vivo imaging.

Accurate detection of hepatic hydrogen sulfide (H2S) to monitor H2S‐related enzymes’ activity is critical for acute hepatitis diagnosis, but remains a challenge due to the dynamic and transient nature of H2S. Here, we report a H2S‐activatable near‐infrared afterglow/MRI bimodal probe F1‐GdNP, which shows an “always‐on” MRI signal and “off‐on” afterglow signal toward H2S. F1‐GdNP shows fast response, high sensitivity and specificity toward H2S, permitting afterglow imaging of H2S and evaluation of cystathionine γ‐lyase (CSE)’s activity in living mice. We further employ the high spatial‐resolution MRI signal of F1‐GdNP to track its delivery and accumulation in liver. Importantly, F1‐GdNP offers a high signal‐to‐background ratio (SBR=86.2±12.0) to sensitively report on the increased hepatic H2S level in the acute hepatitis mice via afterglow imaging, which correlated well with the upregulated CSE activity in the liver, showcasing the good potential of F1‐GdNP for monitoring of acute hepatitis process in vivo.