Targeting Warburg effect to rescue the suffocated photodynamic therapy: A cancer-specific solution.

The cancer photodynamic therapy (PDT) is limited by a congenital defect, namely the tumor hypoxia. Cancer cells are characterized by the vigorous oxygen-consuming glycolysis, which is well-known as the "Warburg effect" and one of the primary causes for the hypoxia. Herein, we employed the glucose metabolism as the cancer-specific target to enhance the performance of PDT. The Salvianolic acid B as the inhibitor of glucose uptake and aerobic glycolysis was concomitantly delivered with the photosensitizer chlorin e6 by a redox-responsive organosilica cross-linked micelle. The results demonstrated that the Salvianolic acid B suppressed the glucose metabolism, retarded the oxygen consumption to retain adequate oxygen as the ammo for PDT, which remarkably improve the efficacy of PDT both in vitro and in vivo. Our study not only provides an alternative strategy to address the hypoxia problem for PDT, but also enhances the selectivity of the treatment by targeting the cancer-specific Warburg effect.

Myocardium-Targeted Micelle Nanomedicine That Salvages the Heart from Ischemia/Reperfusion Injury.

Cardioprotective medication is the common treatment to relieve myocardial ischemia/reperfusion (I/R) injury. However, limited by the low bioavailability of therapeutic drugs, the therapeutic outcome is barely satisfactory. Because the I/R injury can enhance the permeability of the vasculature and allow the extravasation of nanoparticles into the surrounding tissue, herein we formulate the cardiotonic drug olprinone (Olp) in cross-linked micelles as the nanomedicine to achieve myocardium-targeted delivery after systematic administration. As a result, the local concentration of Olp in the injured myocardium is raised by orders of magnitude with prolonged drug duration time. The treatment successfully preserves the pumping efficiency of the heart, alleviates ventricular remodeling, and thus stops the positive feedback loop for the deteriorated cardiac function. Consequently, the myocardium-targeted nanomedicine significantly salvages the heart from I/R injury before irreversible pathological changes take place.

Sensing and imaging of PPi in vivo using lanthanide-based second near-infrared luminescent probes.

Inorganic pyrophosphate (PPi), as a biologically active anion, is closely related to physiological activities and several pathological changes. Here, we reported a luminescent nanoprobe for the detection and imaging of PPi in vivo based on lanthanide nanoparticles with luminescence at the second near-infrared window modified by the tannic acid and Fe3+ complex. A light-harvesting complex was formed after the coordination of colorless tannic acid with Fe3+ and the luminescence of the nanoparticles was quenched through the inner-filter effect. In the presence of PPi, the complex was decomposed due to the stronger coordination affinity of PPi to Fe3+; thus the luminescence of the nanoprobe was recovered. The nanoprobe manifested good linearity with a low detection limit of 3.36 µM. Importantly, in the in vivo study simulating the calcium pyrophosphate deposition disease, the nanoprobe with the second near-infrared luminescence achieved the imaging of the injected PPi at the paw of the mice at a dose of 0.25 mg kg-1. The reported nanoprobe can serve as a convenient tool for the in vivo imaging of PPi and the diagnosis of PPi-related diseases.

A simple paper-based ratiometric luminescent sensor for tetracyclines using copper nanocluster-europium hybrid nanoprobes.

Tetracyclines (TCs), as one of the broad-spectrum antibiotics, are widely used to treat bacterial infections. The residues of TCs in animal-origin foods and drinking water have raised safety concerns and affected the public health. Thus, there is a high demand to develop a simple and rapid method for the detection of TCs. In this work, we developed a ratiometric luminescence probe for the sensitive and visualized detection of TCs. Specifically, tannic acid-stabilized copper nanoclusters (TA-CuNCs) with blue emission at 433 nm were synthesized. The luminescence of TA-CuNCs attenuated partially by the europium ions (Eu3+) due to the aggregation-induced quenching. When TCs were added to the TA-CuNCs-Eu3+ system, the luminescence of TA-CuNCs at 433 nm can be further quenched by the inner-filter effect, and the characteristic luminescence of Eu3+ at 617 nm emerged due to the formation of Eu3+-TCs complex. The ratio of the luminescence at 617 nm-433 nm increased linearly to the concentration of TCs. Additionally, we demonstrated the detection of oxytetracycline in real samples such as tap and lake water, milk, pharmaceutical industry wastewater, honey and soil extract with high recovery rate (97.25%-103.44%). Furthermore, a portable paper device is fabricated by the luminescent probe to conduct the on-site analysis of TCs.

Real-Time Imaging of Hepatic Inflammation Using Hydrogen Sulfide-Activatable Second Near-Infrared Luminescent Nanoprobes.

The sensing and visualized monitoring of hydrogen sulfide (H2S) in vivo is crucial to understand its physiological and pathological roles in human health and diseases. Common methods for H2S detection require the destruction of the biosamples and are not suitable to be applied in vivo. In this Communication, we report a "turn-on" second near-infrared (NIR-II) luminescent approach for sensitive, real-time, and in situ H2S detection, which is based on the absorption competition between the H2S-responsive chromophores (compound 1) and the NIR-II luminescent lanthanide nanoparticles. Specifically, the luminescence was suppressed by compound 1 due to the competitive absorption of the incident light. In the presence of H2S, the compound 1 was bleached to recover the luminescence. Thanks to the deep tissue penetration depth and the low absorbance/scattering on biological samples of the NIR-II nanoprobes, the monitoring of the endogenous H2S in lipopolysaccharide-induced liver inflammation was achieved, which is unattainable by the conventional histopathological and serological approaches.

A General Strategy for Hollow Metal-Phytate Coordination Complex Micropolyhedra Enabled by Cation Exchange.

The ability to incorporate functional metal ions (Mn+ ) into metal-organic coordination complexes adds remarkable flexibility in the synthesis of multifunctional organic-inorganic hybrid materials with tailorable electronic, optical, and magnetic properties. We report the cation-exchanged synthesis of a diverse range of hollow Mn+ -phytate (PA) micropolyhedra via the use of hollow Co2+ -PA polyhedral networks as templates at room temperature. The attributes of the incoming Mn+ , namely Lewis acidity and ionic radius, control the exchange of the parent Co2+ ions and the degree of morphological deformation of the resulting hollow micropolyhedra. New functions can be obtained for both completely and partially exchanged products, as supported by the observation of Ln3+ (Ln3+ =Tb3+ , Eu3+ , and Sm3+ ) luminescence from as-prepared hollow Ln3+ -PA micropolyhedra after surface modification with dipicolinic acid as an antenna. Moreover, Fe3+ - and Mn2+ -PA polyhedral complexes were employed as magnetic contrast agents.

MTH1 inhibitor amplifies the lethality of reactive oxygen species to tumor in photodynamic therapy.

Although photodynamic therapy (PDT) has been clinically applied tumor hypoxia still greatly restricts the performance of this oxygen-dependent oncological treatment. The delivery of oxygen donors to tumor may produce excessive reactive oxygen species (ROS) and damage the peripheral tissues. Herein, we developed a strategy to solve the hypoxia issue by enhancing the lethality of ROS. Before PDT, the ROS-defensing system of the cancer cells was obstructed by an inhibitor to MTH1, which is a key for the remediation of ROS-caused DNA damage. As a result, both nuclei and mitochondrial DNA damages were increased, remarkably promoting cellular apoptosis. The therapeutic results demonstrated that the performance of PDT can be improved by the MTH1 inhibitor, leading to efficient cancer cell killing effect in the hypoxic tumor. This strategy makes better use of the limited oxygen, holding the promise to achieve satisfactory therapeutic effect by PDT without generating redundant cytotoxic ROS.

Gold nanoparticle-based detection of dopamine based on fluorescence resonance energy transfer between a 4-(4-dialkylaminostyryl)pyridinium derived fluorophore and citrate-capped gold nanoparticles.

A colorimetric/fluorometric dual-signal assay is described for the determination of dopamine (DA). A nanoprobe was obtained by linking a 4-(4-dialkylaminostyryl)pyridinium derived fluorophore to citrate-capped gold nanoparticles (AuNPs). The fluorescence of the fluorophore is quenched by the AuNPs via fluorescence resonance energy transfe. In the presence of DA, the catechol group of DA can absorb on the surface of AuNPs to induce aggregation, which is accompanied by a color change from red to blue. The yellow fluorescence of the fluorophore with excitation/emission maximum at 365/570 nm is recovered. The dual-signal detection allows the quantitative analysis of DA within 300 µM by the colorimetric method and 80 µM by the fluorometric method. The detection limits for the colorimetric/fluorometric methods are 1.85 µM and 0.29 µM, respectively. Quantitative determination of DA in spiked urine samples was successfully demonstrated, with recoveries ranging from 98.2 to 106.0%. Graphical abstract A colorimetric/fluorometric dual-signal assay is described for the determination of dopamine by linking a fluorophore to gold nanoparticles. The dopamine causes aggregation of the nanoparticles to induce color change, which is followed by the recovery of the fluorescence.

A simple and rapid fluorescent approach for flavonoids sensor based on gold nanoclusters.

The development of simple, easy-to-operate and real-time detection methods for the active ingredients in herbal medicines has aroused growing interest owing to their pivotal health benefits. In this study, a qualitative and quantitative detection method for the flavonoids was developed based on the specific interaction between flavonoids and bovine serum albumin (BSA). A fluorescent gold nanocluster was imbedded into the cavity enclosed in the tertiary structure of BSA, the fluorescence of which can be quenched by the flavonoids with fast response (<5 s). This decrease in fluorescence intensity of BSA-AuNCs as output signal enables the real-time visual inspection of flavonoids. We demonstrated that the present approach was capable of detecting quercetin in serum, plasma, and monitoring the content of flavonoids in proprietary Chinese medicine Rutin Tablets. BSA-AuNCs was the first fluorescent probe for the specific determination of active ingredients in herbal medicines. Hence the reported protein-AuNCs sensing platform can serve as a convenient detection strategy in pharmaceutical analysis.