The mitochondrial pool of Hsp90 and its mitochondrial paralogue, TRAP1, suppresses cell death and reprograms energy metabolism in cancer cells; therefore, Hsp90 and TRAP1 have been suggested as target proteins for anticancer drug development. Here, we report that the actual target protein in cancer cell mitochondria is TRAP1, and current Hsp90 inhibitors cannot effectively inactivate TRAP1 because of their insufficient accumulation in the mitochondria. To develop mitochondrial TRAP1 inhibitors, we determined the crystal structures of human TRAP1 complexed with Hsp90 inhibitors. The isopropyl amine of the Hsp90 inhibitor PU-H71 was replaced with the mitochondria-targeting moiety triphenylphosphonium to produce SMTIN-P01. SMTIN-P01 showed a different mode of action from the nontargeted PU-H71, as well as much improved cytotoxicity to cancer cells. In addition, we determined the structure of a TRAP1-adenylyl-imidodiphosphate (AMP-PNP) complex. On the basis of comparative analysis of TRAP1 structures, we propose a molecular mechanism of ATP hydrolysis that is crucial for chaperone function.

An adj-dicarbacorrole with CCNN in the core is achieved by replacing the bipyrrole moiety by a simple polycyclic aromatic hydrocarbon, such as biphenyl unit. Spectroscopic studies and structural analyzes confirm the absence of macrocyclic aromatization, thus leading to overall nonaromatic character. The trianionic core is effectively utilized to stabilize a copper(III) ion to form an organocopper complex.

A water-soluble derivative of N-confused porphyrin (NCP) was synthesized, and the photodynamic therapeutic (PDT) application was investigated by photophysical and in vitro studies. High singlet oxygen quantum yield in water at longer wavelength and promising IC(50) values in a panel of cancer cell lines ensure the potential candidacy of the sensitizer as a PDT drug. Reactive oxygen species (ROS) generation on PDT in MDA-MB 231 cells and the apoptotic pathway of cell death was illustrated using different techniques.

Herein, we introduce an indocyanine derivative (IR-Pyr) that is highly water soluble, exhibiting higher mitochondrial targetability and better photostability than IR-780.

Advances in water-insoluble drug delivery systems are limited by selective delivery, loading capacity, and colloidal and encapsulation stability. We have developed a simple and robust hydrophobic-drug delivery platform with different types of hydrophobic chemotherapeutic agents using a noncovalent gatekeeper's technique with mesoporous silica nanoparticles (MSNs). The unmodified pores offer a large volume of drug loading capacity, and the loaded drug is stably encapsulated until it enters the cancer cells owing to the noncovalently bound polymer gatekeeper. In the presence of polymer gatekeepers, the drug-loaded mesoporous silica nanoparticles showed enhanced colloidal stability. The simplicity of drug encapsulation allows any combination of small chemotherapeutics to be coencapsulated and thus produce synergetic therapeutic effects. The disulfide moiety facilitates decoration of the nanoparticles with cysteine containing ligands through thiol-disulfide chemistry under mild conditions. To show the versatility of drug targeting to cancer cells, we decorated the surface of the shell-cross-linked nanoparticles with two types of peptide ligands, SP94 and RGD. The nanocarriers reported here can release encapsulated drugs inside the reducing microenvironment of cancer cells via degradation of the polymer shell, leading to cell death.

In the corrole homologue, 6,11,16-triarylbipyricorrole, the bipyrrole unit is replaced by a 2,2'-bipyridine unit. This modification effectively alters the corrole N4 coordination sphere from the trianionic [(NH)3 N] to the monoanionic [N3NH] state. The newly formed monoanionic core stabilizes Zn(II) ions with enhanced emission properties. The enhanced emission was further utilized for metal ion sensing studies and exploited for the selective detection of Zn(II) ions.

Gastro-intestinal function plays a vital role in conditions ranging from inflammatory bowel disease and HIV through to sepsis and malnutrition. However, the techniques that are currently used to assess gut function are either highly invasive or unreliable. Here we present an alternative, non-invasive sensing modality for assessment of gut function based on fluorescence spectroscopy. In this approach, patients receive an oral dose of a fluorescent contrast agent and a fibre-optic probe is used to make fluorescence measurements through the skin. This provides a readout of the degree to which fluorescent dyes have permeated from the gut into the blood stream. We present preliminary results from our first measurements in human volunteers demonstrating the potential of the technique for non-invasive monitoring of multiple aspects of gastro-intestinal health.

meso-Tetraarylporphycenes, structural isomers of meso-tetraarylporphyrins, were synthesized by the acid-catalyzed oxidative coupling reaction for the first time which is an alternative synthetic methodology to the traditional McMurry coupling reaction. The structure of the macrocycle and Ni(II) complex are characterized by single-crystal X-ray diffraction analyses where both form 1-D supramolecular assembly.