The efficacy of photodynamic therapyi st ypically reliant on the local concentration and diffusion of oxygen. Due to the hypoxic microenvironment found in solid tumors, oxygen-independent photosensitizers are in great demand for cancer therapy. We herein report an iridium(III) anthraquinone complex as am itochondrion-localized carbon-radical initiator.I ts emission is turned on under hypoxic conditions after reduction by reductase.F urthermore,i ts two-photon excitation properties (l ex = 730 nm) are highly desirable for imaging.U pon irradiation, the reduced form of the complex generates carbon radicals,l eading to al oss of mitochondrial membrane potential and cell death (IC 50 light = 2.1 mm,IC 50 dark = 58.2 mm,P I= 27.7). The efficacy of the complex as aP DT agent was also demonstrated under hypoxic conditions in vivo. To the best of our knowledge,i ti st he first metal-complexbased theranostic agent which can generate carbon radicals for oxygen-independent two-photon photodynamic therapy.

Reported is the FeIII‐activated lysosome‐targeting prodrug FerriIridium for gastric cancer theranostics. It contains a meta‐imino catechol group that can selectively bond to, and be oxidized by, free FeIII inside the cell. Subsequent oxidative rearrangement releases FeII and hydrolyses the amine bond under acidic conditions, forming an aminobipyridyl Ir complex and 2‐hydroxybenzoquinone. Thus, FeII catalyzes the Fenton reaction, transforming hydrogen peroxide into hydroxyl radicals, the benzoquinone compounds interfere with the respiratory chain, and conversion of the prodrug into the Ir complex leads to an increase in phosphorescence and toxicity. These properties, combined with the high FeIII content and acidity of cancer cells, make FerriIridium a selective and efficient theranostic agent (IC50=9.22 μm for AGS cells vs. >200 μm for LO2 cells). FerriIridium is the first metal‐based compound that has been developed for chemotherapy using FeIII to enhance both selectivity and potency.

The efficacy of photodynamic therapyi st ypically reliant on the local concentration and diffusion of oxygen. Due to the hypoxic microenvironment found in solid tumors, oxygen-independent photosensitizers are in great demand for cancer therapy. We herein report an iridium(III) anthraquinone complex as am itochondrion-localized carbon-radical initiator.I ts emission is turned on under hypoxic conditions after reduction by reductase.F urthermore,i ts two-photon excitation properties (l ex = 730 nm) are highly desirable for imaging.U pon irradiation, the reduced form of the complex generates carbon radicals,l eading to al oss of mitochondrial membrane potential and cell death (IC 50 light = 2.1 mm,IC 50 dark = 58.2 mm,P I= 27.7). The efficacy of the complex as aP DT agent was also demonstrated under hypoxic conditions in vivo. To the best of our knowledge,i ti st he first metal-complexbased theranostic agent which can generate carbon radicals for oxygen-independent two-photon photodynamic therapy.

Atrial natriuretic peptide (ANP)-mediated natriuresis is known as a cardiac endocrine function in sodium and body fluid homeostasis. Corin is a protease essential for ANP activation. Here, we studied the role of renal corin in regulating salt excretion and blood pressure. We created corin conditional knockout (cKO), in which the Corin gene was selectively disrupted in the kidney (kcKO) or heart (hcKO). We examined the blood pressure, urinary Na+ and Cl− excretion, and cardiac hypertrophy in wild-type, corin global KO, kcKO, and hcKO mice fed normal- and high-salt diets. We found that on a normal-salt diet (0.3% NaCl), corin kcKO and hcKO mice had increased blood pressure, indicating that both renal and cardiac corin is necessary for normal blood pressure in mice. On a high-salt diet (4% NaCl), reduced urinary Na+ and Cl− excretion, increased body weight, salt-exacerbated hypertension, and cardiac hypertrophy were observed in corin kcKO mice. In contrast, impaired urinary Na+ and Cl− excretion and salt-exacerbated hypertension were not observed in corin hcKO mice. These results indicated that renal corin function is important in enhancing natriuresis upon high salt intakes and that this function cannot be compensated by the cardiac corin function in mice.

Drug cocrystals and salts have promising applications for modulating the physicochemical properties and solubility of pharmaceuticals. In this study, a cocrystal and two salts of febuxostat (FEB) with pyridine nitrogen coformers, including 4, 4′-bipyridine (BIP), 3-aminopyridine (3AP) and 4-hydroxypyridine (4HP), were designed to improve the solubility of FEB. The single-crystal structures were elucidated, and their physical and chemical properties were investigated by IR, PXRD, and DSC. In addition, drug-related properties, including the solubility and powder dissolution rate were assessed. The solubility and powder dissolution studies showed that the FEB-BIP cocrystal and FEB-3AP salt have superior dissolution compared to FEB.