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Fluorescence imaging in the second near-infrared (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. Ministry of Education (MOE) National Research Foundation (NRF) The authors thank the financial support from National Natural Science Foundation of China (22106115, 81901803, and 22274107), Jiangsu Specially Appointed Professorship, Natural Science Foundation of Jiangsu Province (BK20190830and BK20190811), Leading Talents of Innovation and Entrepreneurship of Gusu (ZXL2021457),and Soochow Technological Project(SYS2020082).K.P. thanks Singapore National Research Foundation(NRF)(NRF-NRFI07-2021-0005), and Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, RT05/20), Academic Research Fund Tier 2 (MOE-T2EP30220-0010; MOE-T2EP30221-0004), for the financial support.

Development of real-time non-invasive imaging probes to assess infiltration and activation of cytotoxic T cells (CTLs) is critical to predict the efficacy of cancer immunotherapy, which however remains challenging. Reported here is an activatable semiconducting polymer nanoprobe (SPNP) for near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging of a biomarker (granzyme B) associated with activation of CTLs. SPNP comprises a semiconducting polymer (SP) conjugated with a granzyme B cleavable and dye-labeled peptide as the side chain, both of which emit NIRF and PA signals. After systemic administration, SPNP passively targets the tumor and in situ reacts with granzyme B to release the dye-labeled peptide, leading to decreased NIRF and PA signals from the dye but unchanged signals from the polymer. Such ratiometric NIRF and PA signals of SPNP correlate well with the expression level of granzyme B and intratumoral population of CTLs. Thus, this study not only presents the first PA probes for in vivo imaging of immune activation but also provides a molecular design strategy that can be generalized for molecular imaging of other immune-related biomarkers. Ministry of Education (MOE) Nanyang Technological University K.P. thanks Nanyang Technological University (Start-Up grant:M4081627) and the Singapore Ministry of Education Academic Research Fund Tier 1 (2019-T1-002-045,RG125/19) and Academic Research Fund Tier 2 (MOE2018-T2-2-042) for the financial support. This work was also supported by the National Natural Science Foundation of China (81703031 and 81672937).

Discriminative detection of invasive and noninvasive breast cancers is crucial for their effective treatment and prognosis. However, activatable probes able to do so in vivo are rare. Herein, we report an activatable polymeric reporter (P-Dex) that specifically turns on near-infrared (NIR) fluorescent and photoacoustic (PA) signals in response to the urokinase-type plasminogen activator (uPA) overexpressed in invasive breast cancer. P-Dex has a renal-clearable dextran backbone that is linked with a NIR dye caged with an uPA-cleavable peptide substrate. Such a molecular design allows P-Dex to passively target tumors, activate NIR fluorescence and PA signals to effectively distinguish invasive MDA-MB-231 breast cancer from noninvasive MCF-7 breast cancer, and ultimately undergo renal clearance to minimize the toxicity potential. Thus, this polymeric reporter holds great promise for the early detection of malignant breast cancer.

Imaging to evaluate tumor-associated neutrophils (TANs) is imperative for cancer immunotherapy but remains challenging. We herein report an activatable semiconducting polymer nanoprobe (SPCy) for near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging of neutrophil elastase (NE), a biomarker of TANs. SPCy comprises a semiconducting polymer conjugated with a hemicyanine (hemi-Cy) dye caged by a NE-cleavable peptide as the side chain. After systemic administration, SPCy passively targets the tumor and reacts with NE to "uncage" the hemi-Cy, leading to enhanced NIRF and PA signals of the hemi-Cy but unchanged signals of the SP. Such NE-activated ratiometric NIRF and enhanced PA signals of SPCy correlate with the intratumoral population of TANs. Thus, this study not only presents the first TAN-specific PA probe, but also provides a general molecular design strategy for PA imaging of other immune-related biomarkers to facilitate screening of cancer immunotherapeutics. Ministry of Education (MOE) This work was supported by the National Key Research and Development Program of China (2021YFA1101500). K.P. thanks Singapore Ministry of Education, Academic Research Fund Tier 1 (2019-T1-002-045, RG125/19, RT05/20) Academic Research Fund Tier 2 (MOE2018-T2-2-042; MOE-T2EP30220-0010) for the financial support.

Early detection of skin diseases is imperative for their effective treatment. However, fluorescence molecular probes that allow this are rare. The first activatable near-infrared (NIR) fluorescent molecular probe is reported for sensitive imaging of keloid cells, skin cells from abnormal scar fibrous lesions. As keloid cells have high expression levels of fibroblast activation protein-alpha (FAPα), the probe (FNP1) is designed to have a caged NIR dye and a FAPα-cleavable peptide substrate linked by a self-immolative segment. FNP1 can quickly and specifically turn on its fluorescence at 710 nm by 45-fold in the presence of FAPα, allowing it to effectively recognize keloid cells from normal skin cells. Integration of FNP1 with a simple microneedle-assisted topical application enables sensitive detection of keloid cells in metabolically-active human skin tissue with a theoretical limit of detection down to 20 000 cells. MOE (Min. of Education, S’pore) Accepted version

An activatable photoacoustic nanoprobe based on a semiconducting oligomer with amplified brightness and pH-sensing capability is developed by taking advantage of nanodoping to simultaneously create both intraparticle photoinduced electron transfer and intramolecular protonation within a single particle. This organic nanoprobe permits noninvasive real-time ratiometric photoacoustic imaging of pH in tumors in living mice through systemic administration at a relatively low dosage.

Photoacoustic (PA) imaging agents detect disease tissues and biomarkers with increased penetration depth and enhanced spatial resolution relative to traditional optical imaging, and thus hold great promise for clinical applications. However, existing PA imaging agents often encounter the issues of slow body excretion and low-signal specificity, which compromise their capability for in vivo detection. Herein, a fluoro-photoacoustic polymeric renal reporter (FPRR) is synthesized for real-time imaging of drug-induced acute kidney injury (AKI). FPRR simultaneously turns on both near-infrared fluorescence (NIRF) and PA signals in response to an AKI biomarker (γ-glutamyl transferase) with high sensitivity and specificity. In association with its high renal clearance efficiency (78% at 24 h post-injection), FPRR can detect cisplatin-induced AKI at 24 h post-drug treatment through both real-time imaging and optical urinalysis, which is 48 h earlier than serum biomarker elevation and histological changes. More importantly, the deep-tissue penetration capability of PA imaging results in a signal-to-background ratio that is 2.3-fold higher than NIRF imaging. Thus, the study not only demonstrates the first activatable PA probe for real-time sensitive imaging of kidney function at molecular level, but also highlights the polymeric probe structure with high renal clearance. Ministry of Education (MOE) Nanyang Technological University K.P. thanks Nanyang Technological University (Start-Up grant: M4081627), Singapore Ministry of Education Academic Research Fund Tier 1 (2017-T1-002-134, RG147/17; 2019-T1-002-045, RG125/19), and Academic Research Fund Tier 2 (MOE2018-T2-2-042) for the financial support. Q.M. thanks National Natural Science Foundation of China (Grant No. 81901803), Jiangsu Specially Appointed Professorship, and Natural Science Foundation of Jiangsu Province (BK20190811).

To mitigate the growing pressure on resource depletion and environment degradation, the development of green processes for the production of renewable energy is highly required. As a class of novel and promising media, ionic liquids (ILs) have shown infusive potential applications in energy production. Aiming to offer a critical overview regarding the new challenges and opportunities of ILs for developing green processes of renewable energy, this article emphasises the role of ILs as catalysts, solvents, or electrolytes in three broadly interesting energy production processes from renewable resources, such as CO2 conversion to fuels and fuel additives, biomass pretreatment and conversion to biofuels, as well as solar energy and energy storage. It is expected that this article will stimulate a generation of new ideas and new technologies in IL-based renewable energy production.

Despite the great potential of photoacoustic imaging in the life sciences, the development of smart activatable photoacoustic probes remains elusive. On page 3662, K. Pu and co-workers report a facile nanoengineering approach based on semiconducting oligomer nano-particles to develop ratiometric photoacoustic probes with amplified brightness and enhanced sensing capability for accurate photoacoustic mapping of pH in the tumors of living mice.

The coupling reaction of aryl chlorides with arylboronic acids was successfully performed in isopropanol (IPA) by using [NiCl(Ph2PCH2CH2OH)2(H2O)]Cl (5), a cationic Ni(II)-complex, as a precatalyst in the absence of a reducing agent. The coupling reaction proceeded smoothly under mild conditions to provide biaryls in satisfactory to excellent yields, and formation of the undesired dechlorination products of aryl chlorides was completely prevented.