Phthalocyanine-loaded graphene nanoplatform for imaging-guided combinatorial phototherapy

Olena Taratula,1 Mehulkumar Patel,2 Canan Schumann,1 Michael A Naleway,1 Addison J Pang,1 Huixin He,2 Oleh Taratula1 1Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA; 2Department of Chemistry, Rutgers University-Newark, Newark, NJ, USA Abstract: We report a novel cancer-targeted nanomedicine platform for imaging and prospect for future treatment of unresected ovarian cancer tumors by intraoperative multimodal phototherapy. To develop the required theranostic system, novel low-oxygen graphene nanosheets were chemically modified with polypropylenimine dendrimers loaded with phthalocyanine (Pc) as a photosensitizer. Such a molecular design prevents fluorescence quenching of the Pc by graphene nanosheets, providing the possibility of fluorescence imaging. Furthermore, the developed nanoplatform was conjugated with poly(ethylene glycol), to improve biocompatibility, and with luteinizing hormone-releasing hormone (LHRH) peptide, for tumor-targeted delivery. Notably, a low-power near-infrared (NIR) irradiation of single wavelength was used for both heat generation by the graphene nanosheets (photothermal therapy [PTT]) and for reactive oxygen species (ROS)-production by Pc (photodynamic therapy [PDT]). The combinatorial phototherapy resulted in an enhanced destruction of ovarian cancer cells, with a killing efficacy of 90%–95% at low Pc and low-oxygen graphene dosages, presumably conferring cytotoxicity to the synergistic effects of generated ROS and mild hyperthermia. An animal study confirmed that Pc loaded into the nanoplatform can be employed as a NIR fluorescence agent for imaging-guided drug delivery. Hence, the newly developed Pc-graphene nanoplatform has the significant potential as an effective NIR theranostic probe for imaging and combinatorial phototherapy. Keywords: graphene nanosheets, phthalocyanine, photothermal therapy, photodynamic therapy, theranostic&nbsp

Meta-substituted Ru(II) rigid rods for sensitization of TiO(2)

Abstract in Undetermined Ruthenium polypyridyl rigid-rod compounds with phenylene-ethynelene (OPE) spacers and an isophthalic acid (Ipa) binding group were synthesized and characterized for sensitization of nanocrystalline TiO(2) (anatase) thin films. Density functional theory predicted that the most stable structure oriented the isophthalic group about 45 degrees from normal to the TiO(2) surface. Comparative experimental studies of meta- and para-isomers revealed small changes in the ground state absorption spectra and very similar excited state and redox properties. The excited state injection yields (inj = 0.15 +/- 0.03)into nanocrystalline TiO(2) and the subsequent charge recombination rates were found to be insensitive to the isomer utilized. Meta-substitution enabled the synthesis of sensitizers with two Ru(II) sensitizers that displayed enhanced sunlight absorption relative to the monomeric compound

Influence of the Electron-Cation Interaction on Electron Mobility in Dye-Sensitized ZnO and TiO2 Nanocrystals: A Study Using Ultrafast Terahertz Spectroscopy

Charge transport and recombination in nanostructured semiconductors are poorly understood key processes in dye-sensitized solar cells. We have employed time-resolved spectroscopies in the terahertz and visible spectral regions supplemented with Monte Carlo simulations to obtain unique information on these processes. Our results show that charge transport in the active solar cell material can be very different from that in nonsensitized semiconductors, due to strong electrostatic interaction between injected electrons and dye cations at the surface of the semiconductor nanoparticle. For ZnO, this leads to formation of an electron-cation complex which causes fast charge recombination and dramatically decreases the electron mobility even after the dissociation of the complex. Sensitized TiO2 does not suffer from this problem due to its high permittivity efficiently screening the charges

DNA Photocleavage in the Near-Infrared Wavelength Range by 2-Quinolinium Dicarbocyanine Dyes

Here, we report the syntheses of two pentamethine cyanine dyes containing quinolinium rings and substituted with either hydrogen (3) or bromine (4) at the meso carbon. The electron withdrawing bromine atom stabilizes dye 4 in aqueous buffer, allowing complex formation to occur between the dye and double-helical DNA. UV–visible, CD, and fluorescence spectra recorded at low DNA concentrations suggest that dye 4 initially binds to the DNA as a high-order aggregate. As the ratio of DNA to dye is increased, the aggregate is converted to monomeric and other low-order dye forms that interact with DNA in a non-intercalative fashion. The brominated dye 4 is relatively unreactive in the dark, but, under 707–759 nm illumination, generates hydroxyl radicals that cleave DNA in high yield (pH 7.0, 22 °C). Dye 4 is also taken up by ES2 ovarian carcinoma cells, where it is non-toxic under dark conditions. Upon irradiation of the ES2 cells at 694 nm, the brominated cyanine reduces cell viability from 100 ± 10% to 14 ± 1%. Our results suggest that 2-quinolinium-based carbocyanine dyes equipped with stabilizing electron withdrawing groups may have the potential to serve as sensitizing agents in long-wavelength phototherapeutic applications