Self-Assembly of Mitochondria-Targeted Photosensitizer to Increase Photostability and Photodynamic Therapeutic Efficacy in Hypoxia

The development of photosensitizers for cancer photodynamic therapy has been challenging due to their low photostability and therapeutic inefficacy in hypoxic tumor microenvironments. To overcome these issues, we have developed a mitochondria-targeted photosensitizer consisting of an indocyanine moiety with triphenylphosphonium arms, which can self-assemble into spherical micelles directed to mitochondria. Self-assembly of the photosensitizer resulted in a higher photostability by preventing free rotation of the indoline ring of the indocyanine moiety. The mitochondria targeting capability of the photosensitizer allowed it to utilize intramitochondrial oxygen. We found that the mitochondria-targeted photosensitizer localized to mitochondria and induced apoptosis of cancer cells both normoxic and hypoxic conditions through generation of ROS. The micellar self-assemblies of the photosensitizer were further confirmed to selectively localize to tumor tissues in a xenograft tumor mouse model through passive targeting and showed efficient tumor growth inhibition.     

A comparison of determination methods for uranium radioactivity in environmental soil samples using a gamma spectrometer

Journal of Radioanalytical and Nuclear Chemistry - Comparisons of statistical analysis results between five methods using gamma spectrometry and a control group for measuring the radioactivity of...     

Set-Wise Differential Interaction between Copy Number Alterations and Gene Expressions of Lower-Grade Glioma Reveals Prognosis-Associated Pathways

The integrative analysis of copy number alteration (CNA) and gene expression (GE) is an essential part of cancer research considering the impact of CNAs on cancer progression and prognosis. In this research, an integrative analysis was performed with generalized differentially coexpressed gene sets (gdCoxS), which is a modification of dCoxS. In gdCoxS, set-wise interaction is measured using the correlation of sample-wise distances with Renyi’s relative entropy, which requires an estimation of sample density based on omics profiles. To capture correlations between the variables, multivariate density estimation with covariance was applied. In the simulation study, the power of gdCoxS outperformed dCoxS that did not use the correlations in the density estimation explicitly. In the analysis of the lower-grade glioma of the cancer genome atlas program (TCGA-LGG) data, the gdCoxS identified 577 pathway CNAs and GEs pairs that showed significant changes of interaction between the survival and non-survival group, while other benchmark methods detected lower numbers of such pathways. The biological implications of the significant pathways were well consistent with previous reports of the TCGA-LGG. Taken together, the gdCoxS is a useful method for an integrative analysis of CNAs and GEs.     

Photophysical Properties and Heterogeneous Photoredox Catalytic Activities of Ru(bpy)3@InBTB Metal–Organic Framework (MOF)

Metal–organic frameworks (MOFs) with negatively charged frameworks are suitable for selectively encapsulating cationic guest ions via a cation-exchange process. Encapsulating photoactive [RuL₃]²⁺ polypyridine complexes into the preorganized mesoscale channels of a MOF is a good method for stabilizing the excited states of the complexes. Three new RuL₃@InBTB MOFs were prepared by encapsulating cationic [Ru(bpy)₃]²⁺ (bpy=2,2′-bipyridine), [Ru(phen)₃]²⁺ (phen=1,10-phenanthroline), and [Ru(bpz)₃]²⁺ (bpz=2,2′-bipyrazine) into the mesopores of a three-dimensional (3D) InBTB MOF (H₃BTB=1,3,5-benzenetribenzoic acid). The photophysical properties of the resulting materials were investigated by photoluminescence (PL) analysis. The photoredox catalytic activities were also investigated for the aza-Henry reaction, hydrogenation of dimethyl maleate, and decomposition of methyl orange under visible light irradiation at room temperature. RuL₃@InBTB MOFs were found to be very stable and highly recyclable photoredox catalytic systems.     

Unidirectional helical assembly via triple hydrogen bonds between chiral tris(oxazoline) and achiral tris(imidazoline)

Tris(imidazolines) are assembled via triple hydrogen bonding interactions to give rise to a stacked polymeric structure. A mixture of chiral tris(oxazoline) and achiral tris(imidazoline) generates a helical assembly in which the helical direction of the assembly is unidirectionally induced by the chirality of tris(oxazoline).     

Synthesis of polyaniline/multiwall carbon nanotube composite via inverse emulsion polymerization

The composite of polyaniline (PANI) and multiwall carbon nanotube carboxylated through acid treatment (c‐MWCNT) was synthesized by chemical oxidative polymerization in an inverse emulsion system. The resultant composites were compared with products from aqueous emulsion polymerization to observe the improvements in electrical conductivity, structural properties, and thermal stability obtained by this synthetic method. Prior to the inverse emulsion polymerization, MWCNT was treated with a strong acid mixture to be functionalized with carboxylic acid groups. Carboxylic acid groups on surfaces induced selective dispersibility between polar and nonpolar solvents because of the increase of hydrophilicity. As the content of c‐MWCNT was increased, the electrical conductivity was increased by a charge transport function from the intrinsic electrical conductivity of MWCNT and the formation of a highly ordered dense structure of PANI molecules on the surface of c‐MWCNT. The images observed with electron spectroscopy showed the capping of c‐MWCNT with PANI. The growth of additional ordered structures of PANI/c‐MWCNT composite, which was observed through wide‐angle X‐ray diffraction patterns, supported the capping by PANI. It was observed that the doping of the composite had a significant relationship with the concentration of dodecylbenzenesulfonic acid (DBSA). The thermal stability of PANI composite was improved by the addition of c‐MWCNT; this was thought to be related with structure ordering by inverse emulsion polymerization. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2255–2266, 2008     

Enhancement of the protein loading density by a pre-cleaning process of a gold substrate: confocal laser scanning microscopic study.

The immobilization of glucose oxidase (GOx), using self assembled monolayers (SAMs) on gold surfaces, was investigated by grazing angle FT-IR spectroscopy, surface plasmon resonance (SPR) spectroscopy, and atomic force microscopy (AFM) in conjunction with confocal laser scanning microscopy (CLSM). To find an optimum condition for the maximum GOx loading density on gold surfaces, different cleaning protocols were examined. The loading density of GOx on surfaces was investigated by AFM and CLSM. In particular, CLSM was more effective for identifying the GOx density than AFM, since its scanning speed is much faster and it covers a larger area. Based on CLSM images of the GOx immobilized on the surfaces, it was concluded that the pre-cleaning process of gold substrates using different solvents, such as acetone, ethanol and 2-propanol, is very important for enhancing the GOx loading density. This result enables us to investigate an effective fabrication process in fabricating biosensors.     

Microencapsulation of cholesteryl alkanoate by polymerization‐induced phase separation and its association with drugs

A new microencapsulation technique is presented in which cholesteryl nonanoate (CN)/poly(methyl methacrylate) (PMMA) microcapsules are produced by the induction of phase separation between CN and PMMA within the droplets during the polymerization. The concentration of CN is the most important factor determining the final morphology of the microcapsules. For example, a polynuclear type is obtained at a low concentration (<20 wt %), a mononuclear type is obtained at a medium concentration (20–30 wt %), and an irregular phase is obtained at a high concentration (>40 wt %). To evaluate the effectiveness of the technique for stabilizing an unstable drug, we selected retinol (vitamin A) as a model drug and loaded it into the CN/PMMA microcapsules. We used a process called solute codiffusion, in which a fine solvent emulsion containing the retinol was diffused uniformly into the CN/PMMA microcapsules. The loading efficiency of retinol was predicted successfully with the aid of a thermodynamic equation. In the thermal stability test of retinol, we found that an effective association with the CN phase was the most important factor determining the limit of its molecular stability. The technique reported in this article has great potential for the microencapsulation of soft materials via a simple process and for the stabilization of unstable drugs. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2202–2213, 2004