Explore the vast range of titles available.

Drug-induced acute kidney injury (AKI) with a high morbidity and mortality is poorly diagnosed in hospitals and deficiently evaluated in drug discovery. Here, we report the development of molecular renal probes (MRPs) with high renal clearance efficiency for in vivo optical imaging of drug-induced AKI. MRPs specifically activate their near-infrared fluorescence or chemiluminescence signals towards the prodromal biomarkers of AKI including the superoxide anion, N-acetyl-β-d-glucosaminidase and caspase-3, enabling an example of longitudinal imaging of multiple molecular events in the kidneys of living mice. Importantly, they in situ report the sequential occurrence of oxidative stress, lysosomal damage and cellular apoptosis, which precedes clinical manifestation of AKI (decreased glomerular filtration). Such an active imaging mechanism allows MRPs to non-invasively detect the onset of cisplatin-induced AKI at least 36 h earlier than the existing imaging methods. MRPs can also act as exogenous tracers for optical urinalysis that outperforms typical clinical/preclinical assays, demonstrating their clinical promise for early diagnosis of AKI.Chemiluminescent molecular renal probes have been developed and are shown to be capable of non-invasive real-time imaging of early-stage oxidative stress biomarkers of drug-induced acute kidney injury, and high renal clearance.

Nanomedicine in combination with immunotherapy offers opportunities to treat cancer in a safe and effective manner; however, remote control of immune response with spatiotemporal precision remains challenging. We herein report a photothermally activatable polymeric pro-nanoagonist (APNA) that is specifically regulated by deep-tissue-penetrating second near-infrared (NIR-II) light for combinational photothermal immunotherapy. APNA is constructed from covalent conjugation of an immunostimulant onto a NIR-II semiconducting transducer through a labile thermo-responsive linker. Upon NIR-II photoirradiation, APNA mediates photothermal effect, which not only triggers tumor ablation and immunogenic cell death but also initiates the cleavage of thermolabile linker to liberate caged agonist for in-situ immune activation in deep solid tumor (8 mm). Such controlled immune regulation potentiates systemic antitumor immunity, leading to promoted cytotoxic T lymphocytes and helper T cell infiltration in distal tumor, lung and liver to inhibit cancer metastasis. Thereby, the present work illustrates a generic strategy to prepare pro-immunostimulants for spatiotemporal regulation of cancer nano-immunotherapy. Precise control of immune response remains challenging for cancer immunotherapy. Here, the authors report on photothermally activatable semiconducting polymeric pro-agonist in response to second near-infrared window light for regulated photothermal immunotherapy.

Optical imaging in disease diagnosis and treatment benefits from high spatiotemporal resolution and the availability of numerous optical agents. However, many optical imaging probes are cleared by the reticuloendothelial system, which can lead to probe accumulation in the liver and spleen and hence organ toxicity. By contrast, renal-clearable optical agents (RCOAs) are rapidly excreted from the body via the kidneys, undergoing minimal metabolism. In this Review, we discuss the design principles of RCOAs, with a focus on imaging and disease theranostics (the combination of diagnosis and therapy). Renal excretion of RCOAs makes them intrinsically suitable for targeted kidney imaging, including passive monitoring of the glomerular filtration rate and detection of early kidney injury biomarkers. The pharmacokinetics of RCOAs can further be tailored to prolong their circulation in the blood, allowing deep tumour penetration and high-contrast tumour imaging. Finally, we discuss intraoperative image-guided surgery and optical urinalysis, and suggest future applications of RCOAs. Intravenously injected renal-clearable optical agents (RCOAs) are rapidly cleared by the kidneys, allowing disease diagnosis and treatment by optical imaging, while avoiding unwanted tissue accumulation and adverse effects. This Review discusses the design of RCOAs for kidney imaging, kidney injury detection, cancer theranostics, intraoperative image-guided surgery and optical urinalysis.

Immunometabolic intervention has been applied to treat cancer via inhibition of certain enzymes associated with intratumoral metabolism. However, small-molecule inhibitors and genetic modification often suffer from insufficiency and off-target side effects. Proteolysis targeting chimeras (PROTACs) provide an alternative way to modulate protein homeostasis for cancer therapy; however, the always-on bioactivity of existing PROTACs potentially leads to uncontrollable protein degradation at non-target sites, limiting their in vivo therapeutic efficacy. We herein report a semiconducting polymer nano-PROTAC (SPN pro ) with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy. SPN pro can remotely generate singlet oxygen ( 1 O 2 ) under NIR photoirradiation to eradicate tumor cells and induce immunogenic cell death (ICD) to enhance tumor immunogenicity. Moreover, the PROTAC function of SPN pro is specifically activated by a cancer biomarker (cathepsin B) to trigger targeted proteolysis of immunosuppressive indoleamine 2,3-dioxygenase (IDO) in the tumor of living mice. The persistent IDO degradation blocks tryptophan (Trp)-catabolism program and promotes the activation of effector T cells. Such a SPNpro-mediated in-situ immunometabolic intervention synergizes immunogenic phototherapy to boost the antitumor T-cell immunity, effectively inhibiting tumor growth and metastasis. Thus, this study provides a polymer platform to advance PROTAC in cancer therapy. Proteolysis targeting chimeras (PROTACs) is an effective alternative to modulate protein homeostasis but can lead to uncontrollable protein degradation and off-target side effects. Here, the authors developed semiconducting polymer nano-PROTACs with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy.

Despite its growing promise in cancer treatment, ferrotherapy has low therapeutic efficacy due to compromised Fenton catalytic efficiency in tumor milieu. We herein report a hybrid semiconducting nanozyme (HSN) with high photothermal conversion efficiency for photoacoustic (PA) imaging-guided second near-infrared photothermal ferrotherapy. HSN comprises an amphiphilic semiconducting polymer as photothermal converter, PA emitter and iron-chelating Fenton catalyst. Upon photoirradiation, HSN generates heat not only to induce cytotoxicity but also to enhance Fenton reaction. The increased ·OH generation promotes both ferroptosis and apoptosis, oxidizes HSN (42 nm) and transforms it into tiny segments (1.7 nm) with elevated intratumoral permeability. The non-invasive seamless synergism leads to amplified therapeutic effects including a deep ablation depth (9 mm), reduced expression of metastasis-related proteins and inhibition of metastasis from primary tumor to distant organs. Thereby, our study provides a generalized nanozyme strategy to compensate both ferrotherapy and phototherapeutics for complete tumor regression. Due to tumour microenvironment, Fenton reactions have low therapeutic efficiency. Here the authors report on the application of NIR-II hybrid semiconducting nanozymes for combined photothermal therapy and enhanced ferrotherapy with photoacoustic imaging and show application in vivo in tumour models.

Afterglow imaging with long-lasting luminescence after cessation of light excitation provides opportunities for ultrasensitive molecular imaging; however, the lack of biologically compatible afterglow agents has impeded exploitation in clinical settings. This study presents a generic approach to transforming ordinary optical agents (including fluorescent polymers, dyes, and inorganic semiconductors) into afterglow luminescent nanoparticles (ALNPs). This approach integrates a cascade photoreaction into a single-particle entity, enabling ALNPs to chemically store photoenergy and spontaneously decay it in an energy-relay process. Not only can the afterglow profiles of ALNPs be finetuned to afford emission from visible to near-infrared (NIR) region, but also their intensities can be predicted by a mathematical model. The representative NIR ALNPs permit rapid detection of tumors in living mice with a signal-to-background ratio that is more than three orders of magnitude higher than that of NIR fluorescence. The biodegradability of the ALNPs further heightens their potential for ultrasensitive in vivo imaging. Afterglow luminescence is used to reduce background noise and increase sensitivity; however, biocompatible afterglow materials are limited. Here, the authors report on an approach to turn standard optical agents into afterglow nanoparticles and demonstrate the application in tumour imagining in vivo.

Molecular probes that change their signals in response to the target of interest have a critical role in fundamental biology and medicine. Semiconducting polymer nanoparticles (SPNs) have recently emerged as a new generation of purely organic photonic nanoagents with desirable properties for biological applications. In particular, tunable optical properties of SPNs allow them to be developed into photoluminescence, chemiluminescence, and photoacoustic probes, wherein SPNs usually serve as the energy donor and internal reference for luminescence and photoacoustic probes, respectively. Moreover, facile surface modification and intraparticle engineering provide the versatility to make them responsive to various biologically and pathologically important substances and indexes including small‐molecule mediators, proteins, pH and temperature. This article focuses on recent advances in the development of SPN‐based activatable molecular probes for sensing and imaging. The designs and applications of these probes are discussed in details, and the present challenges to further advance them into life science are also analyzed. Semiconducting polymer nanoparticles (SPNs) have shown great promise in life science. Recent advances of developing SPNs into smart activatable probes for biological sensing and molecular imaging are discussed.

Optical nanoparticles are promising diagnostic tools; however, their shallow optical imaging depth and slow clearance from the body have impeded their use for in vivo disease detection. To address these limitations, we develop activatable polyfluorophore nanosensors with biomarker-triggered nanoparticle-to-molecule pharmacokinetic conversion and near-infrared fluorogenic turn-on response. Activatable polyfluorophore nanosensors can accumulate at the disease site and react with disease-associated proteases to undergo in situ enzyme-catalysed depolymerization. This disease-specific interaction liberates renal-clearable fluorogenic fragments from activatable polyfluorophore nanosensors for non-invasive longitudinal urinalysis and outperforms the gold standard blood and urine assays, providing a level of sensitivity and specificity comparable to those of invasive biopsy and flow cytometry analysis. In rodent models, activatable polyfluorophore nanosensors enable ultrasensitive detection of tumours (1.6 mm diameter) and early diagnosis of acute liver allograft rejection. We anticipate that our modular nanosensor platform may be applied for early diagnosis of a range of diseases via a simple urine test. Early cancer detection typically involves invasive biopsies. Here the authors designed nanosensors that are depolymerized by disease-associated enzymes in vivo to produce fluorescent urinary signals for non-invasive early diagnosis.

Checkpoint immunotherapies have been combined with other therapeutic modalities to increase patient response rate and improve therapeutic outcome, which however exacerbates immune-related adverse events and requires to be carefully implemented in a narrowed therapeutic window. Strategies for precisely controlled combinational cancer immunotherapy can tackle this issue but remain lacking. We herein report a catalytical nano-immunocomplex for precise and persistent sono-metabolic checkpoint trimodal cancer therapy, whose full activities are only triggered by sono-irradiation in tumor microenvironment (TME). This nano-immunocomplex comprises three FDA-approved components, wherein checkpoint blockade inhibitor (anti-programmed death-ligand 1 antibody), immunometabolic reprogramming enzyme (adenosine deaminase, ADA), and sonosensitizer (hematoporphyrin) are covalently immobilized into one entity via acid-cleavable and singlet oxygen-activatable linkers. Thus, the activities of the nano-immunocomplex are initially silenced, and only under sono-irradiation in the acidic TME, the sonodynamic, checkpoint blockade, and immunometabolic reprogramming activities are remotely awakened. Due to the enzymatic conversion of adenosine to inosine by ADA, the nano-immunocomplex can reduce levels of intratumoral adenosine and inhibit A2A/A2B adenosine receptors-adenosinergic signaling, leading to efficient activation of immune effector cells and inhibition of immune suppressor cells in vivo. Thus, this study presents a generic and translatable nanoplatform towards precision combinational cancer immunotherapy. Ultrasound-based therapies in combination with immune checkpoint blockade have been shown to improve the efficacy of cancer immunotherapy. Here the authors report the design of a pH-responsive and sono-irradiation activatable nanosystem functionalized with anti-PD-L1 and adenosine deaminase for sono-metabolic cancer immunotherapy.

Optical imaging probes allow us to detect and uncover the physiological and pathological functions of an analyte of interest at the molecular level in a non-invasive, longitudinal manner. By virtue of simplicity, low cost, high sensitivity, adaptation to automated analysis, capacity for spatially resolved imaging and diverse signal output modes, optical imaging probes have been widely applied in biology, physiology, pharmacology and medicine. To build a reliable and practically/clinically relevant probe, the design process often encompasses multidisciplinary themes, including chemistry, biology and medicine. Within the repertoire of probes, dual-locked systems are particularly interesting as a result of their ability to offer enhanced specificity and multiplex detection. In addition, chemiluminescence is a low-background, excitation-free optical modality and, thus, can be integrated into dual-locked systems, permitting crosstalk-free fluorescent and chemiluminescent detection of two distinct biomarkers. For many researchers, these dual-locked systems remain a ‘black box’. Therefore, this Review aims to offer a ‘beginner’s guide’ to such dual-locked systems, providing simple explanations on how they work, what they can do and where they have been applied, in order to help readers develop a deeper understanding of this rich area of research. Dual-locked optical probes change their optical signals when they respond to two biomarkers of interest. This facilitates real-time imaging of multiple interrelated biomarkers in living systems and, thus, provides opportunities to better understand pathological events and enhanced diagnostic specificity.