“Four-In-One” Design of a Hemicyanine-Based Modular Scaffold for High-Contrast Activatable Molecular Afterglow Imaging

Afterglow luminescence (long persistent luminescence) holds great potential for nonbackground molecular imaging. However, current afterglow probes are mainly nanoparticles, and afterglow imaging systems based on organic small molecules are still lacking and have rarely been reported. Moreover, the lack of reactive sites and a universal molecular scaffold makes it difficult to design activatable afterglow probes. To address these issues, this study reports a novel kind of hemicyanine-based molecule scaffolds with stimuli-responsive afterglow luminescence, which is dependent on an intramolecular cascade photoreaction between 1O2 and the afterglow molecule to store the photoenergy for delayed luminescence after light cessation. As a proof of concept, three modular activatable molecular afterglow probes (MAPs) with a “four-in-one” molecular design by integrating a stimuli-responsive unit, 1O2-generating unit, 1O2-capturing unit, and luminescent unit into one probe are customized for quantification and imaging of targets including pH, superoxide anions, and aminopeptidase. Notably, MAPs show higher sensitivity in afterglow imaging than in fluorescence imaging because the responsive unit simultaneously controls the initiation of fluorescence (S1 to S0) and 1O2 generation (S1 to T1). Finally, MAPs are applied for high-contrast afterglow imaging of drug-induced hepatotoxicity, which is poorly evaluated in clinics and drug discovery. By reporting the sequential occurrence of oxidative stress and upregulation of aminopeptidase, such activatable afterglow probes allow noninvasive imaging of hepatotoxicity earlier than the serological and histology manifestation, indicating their promise for early diagnosis of hepatotoxicity

A Magneto-Optical Nanoplatform for Multimodality Imaging of Tumors in Mice

Multimodality imaging involves the use of more imaging modes to image the same living subjects and is now generally preferred in clinics for cancer imaging. Here we present multimodalityMagnetic Particle Imaging (MPI), Magnetic Resonance Imaging (MRI), Photoacoustic, Fluorescentnanoparticles (termed MMPF NPs) for imaging tumor xenografts in living mice. MMPF NPs provide long-term (more than 2 months), dynamic, and accurate quantification, in vivo, of NPs and in real time by MPI. Moreover, MMPF NPs offer ultrasensitive MPI imaging of tumors (the tumor ROI increased by 30.6 times over that of preinjection). Moreover, the nanoparticle possessed a long-term blood circulation time (half-life at 49 h) and high tumor uptake (18% ID/g). MMPF NPs have been demonstrated for imaging breast and brain tumor xenografts in both subcutaneous and orthotopic models in mice via simultaneous MPI, MRI, fluorescence, and photoacoustic imaging with excellent tumor contrast to normal tissues

A Magneto-Optical Nanoplatform for Multimodality Imaging of Tumors in Mice

Multimodality imaging involves the use of more imaging modes to image the same living subjects and is now generally preferred in clinics for cancer imaging. Here we present multimodalityMagnetic Particle Imaging (MPI), Magnetic Resonance Imaging (MRI), Photoacoustic, Fluorescentnanoparticles (termed MMPF NPs) for imaging tumor xenografts in living mice. MMPF NPs provide long-term (more than 2 months), dynamic, and accurate quantification, in vivo, of NPs and in real time by MPI. Moreover, MMPF NPs offer ultrasensitive MPI imaging of tumors (the tumor ROI increased by 30.6 times over that of preinjection). Moreover, the nanoparticle possessed a long-term blood circulation time (half-life at 49 h) and high tumor uptake (18% ID/g). MMPF NPs have been demonstrated for imaging breast and brain tumor xenografts in both subcutaneous and orthotopic models in mice via simultaneous MPI, MRI, fluorescence, and photoacoustic imaging with excellent tumor contrast to normal tissues

MoS₂‑Based Nanoprobes for Detection of Silver Ions in Aqueous Solutions and Bacteria

Silver as an extensively used antibacterial agent also poses potential threats to the environment and human health. Hence, in this work, we design a fluorescent nanoprobe by using rhodamine B isothiocyanate (RhoBS) adsorbed MoS₂ nanosheets to realize sensitive and selective detection of Ag⁺. On the surface of RhoBS-loaded MoS₂ nanosheets, Ag⁺ can be reduced to Ag nanoparticles, which afterward could not only lead to the detachment of RhoBS molecules and thus their recovered fluorescence but also the surface-enhanced fluorescence from RhoBS remaining adsorbed on MoS₂. Such an interesting mechanism allows highly sensitive detection of Ag⁺ (down to 10 nM) with great selectivity among other metal ions. Moreover, we further demonstrate that our MoS₂–RhoBS complex could act as a nontoxic nanoprobe to detect Ag⁺ in live bacteria samples. Our work resulted from an unexpected finding and suggests the promise of two-dimensional transition-metal sulfide nanosheets as a novel platform for chemical and biological sensing

Nanoscale Metal–Organic Framework Based Two-Photon Sensing Platform for Bioimaging in Live Tissue

Nanoscale metal–organic frameworks (NMOFs) have been applied for biomedical sensing in recent years. However, it is still a great challenge to construct a highly efficient NMOFs fluorescent probe for sensing in a biological system, with high signal-to-noise ratio, photostability, and deep tissue penetration. Herein, for the first time, we report the two-photon metal–organic framework (TP-MOF) as a sensing platform. The design of TP-MOF is based on NMOFs incorporating a target-responsive two-photon organic moiety through click chemistry. PCN-58, as a model building block, was covalently modified with a small-molecule probe for H2S or Zn2+ as model analytes. TP-MOF probes retain the fluorescence-responsive properties of the TP organic moiety and possess excellent photostability and selectivity, as well as biocompatibility. Benefiting from the near-infrared (∼820 nm) excited two-photon fluorophore, TP-MOF probes serve to sense and image their respective targets in live cells and tissue slices with a penetration of 130 μm. The molecular design presented here bodes well for the extension to other MOFs displaying sensing components for other analytes of interest

Semiconducting Polymer Nanoparticles-Manganese Based Chemiluminescent Platform for Determining Total Antioxidant Capacity in Diabetic Mice

The total antioxidant capacity (TAC) is a key indicator of the body’s resistance to oxidative stress injury in diabetic patients. The measurement of TAC is important for effectively evaluating the redox state to prevent and control the occurrence of diabetes complications. However, there is a lack of a simple, convenient, and reliable method to detect the total antioxidant capacity in diabetes. Herein, we design a novel chemiluminescent platform based on semiconducting polymer nanoparticles-manganese (SPNs-MnVII) to detect the total antioxidant capacity of urine in diabetic mice. We synthesize semiconducting polymer nanoparticles with four different structures and discover the ability of MnVII to produce singlet oxygen (1O2) that is employed to excite thiophene-based SPNs (PFODBT) to emit near-infrared chemiluminescence. Notably, the chemiluminescent intensity has a good linear relationship with the concentration of MnVII (detection limit: 2.8 μM). Because antioxidants (e.g., glutathione or ascorbic acid) can react with MnVII, such a chemiluminescent tool of SPNs (PFODBT)-MnVII can detect the glutathione or ascorbic acid with a larger responsive range. Furthermore, the total antioxidant capacity of urine from mice is evaluated via SPNs (PFODBT)-MnVII, and there are statistically significant differences between diabetic and healthy mice. Thus, this new chemiluminescent platform of SPNs (PFODBT)-MnVII is convenient, efficient, and sensitive, which is promising for monitoring antioxidant therapy of diabetes

Specific Core–Satellite Nanocarriers for Enhanced Intracellular ROS Generation and Synergistic Photodynamic Therapy

The deficiency of reactive oxygen species (ROS) is the main reason for the current poor efficiency of tumor photodynamic therapy (PDT). To solve this problem, a simple light-triggered core–satellite nanoplatform (UPSD@Au) has been developed by loading Au nanoparticles on the surface of mesoporous silica-coated upconversion nanoparticles. Small molecules DC50 (C17H14BrF2N3OS) and photosensitizer (silicon phthalocyanine dihydroxide, SPCD) were loaded into the silica shell to improve ROS production. Meanwhile, PDT can be triggered through facile near-infrared laser irradiation given the occurrence of a moderate photothermal transfer process between upconversion nanoparticles and Au. The reasonable increment in temperature induced by Au resulted in the timely release of DC50. The inhibition of copper transfer by DC50 results in reduced ROS scavenging and thus improves light-triggered ROS accumulation. Notably, the expression levels of the human copper-trafficking proteins Atox1 and CCS in cancerous cells exceed those in normal cells, and thus enhanced ROS accumulation effect was achieved in cancerous cells. In vitro and in vivo results demonstrate that the synergism between DC50 and SPCD coloaded in the UPSD@Au nanoplatform increases the efficiency of PDT. The UPSD@Au platform represents an efficient codelivery method for hydrophobic small molecules and improves sensitization to specific cancer therapy