Photosensitizer Drug Delivery via an Optical Fiber

: An optical fiber has been developed with a maneuverable miniprobe tip that sparges O2 gas and photodetaches pheophorbide (sensitizer) molecules. Singlet oxygen is produced at the probe tip surface which reacts with an alkene spacer group releasing sensitizer upon fragmentation of a dioxetane intermediate. Optimal sensitizer photorelease occurred when the probe tip was loaded with 60 nmol sensitizer, where crowding of the pheophorbide molecules and self-quenching were kept to a minimum. The fiber optic tip delivered pheophorbide molecules and singlet oxygen to discrete locations. The 60 nmol sensitizer was delivered into petrolatum; however, sensitizer release was less efficient in toluene-d8 (3.6 nmol) where most had remained adsorbed on the probe tip, even after the covalent alkene spacer bond had been broken. The results open the door to a new area of fiber optic-guided sensitizer delivery for the potential photodynamic therapy of hypoxic structures requiring cytotoxic control

"Pointsource" Delivery of a Photosensitizer Drug and Singlet Oxygen: Eradication of Glioma Cells In Vitro

ABSTRACT We describe a pointsource sensitizer-tipped microoptic device for the eradication of glioma U87 cells. The device has a mesoporous fluorinated silica tip which emits singlet oxygen molecules and small quantities of pheophorbide sensitizer for additional production of singlet oxygen in the immediate vicinity. The results show that the device surges in sensitizer release and photokilling with higher rates about midway through the reaction. This was attributed to a self-amplified autocatalytic reaction where released sensitizer in the extracellular matrix provides positive feedback to assist in the release of additional sensitizer. The photokilling of the glioma cells was analyzed by global toxicity and live/dead assays, where a killing radius around the tip with~0.3 mm precision was achieved. The implication of these results for a new PDT tool of hard-to-resect tumors, e.g. in the brain, is discussed

REVIEW PAPER ON EFFECT OF ALUMINIUM DROSS ON PROPERTIES OF CONCRETE

The Bhima River is a main river in South India. It flows southeast for 861 kilometers (535 mi) through Maharashtra, Karnataka, and Telangana states, before inflowing the Krishna River. Along the river stretch there are about 7000 industries comprise Large, middling and little scale units according to CPCB. Most of the industry are located in the Maharashtra Industrial enlargement Corporation (MIDC). The river is 70% polluted by industries pollution and 30% by domestic wastewater. The following decision article presents the termination of the work approved out by the researchers in the past on the various River wate

“Ene” Reactions of Singlet Oxygen at the Air–Water Interface

Prenylsurfactants [(CH₃)₂CCH­(CH₂)_<i>n</i>SO₃^– Na⁺ (<i>n</i> = 4, 6, or 8)] were designed to probe the “ene” reaction mechanism of singlet oxygen at the air–water interface. Increasing the number of carbon atoms in the hydrophobic chain caused an increase in the regioselectivity for a secondary rather than tertiary surfactant hydroperoxide, arguing for an orthogonal alkene on water. The use of water, deuterium oxide, and H₂O/D₂O mixtures helped to distinguish mechanistic alternatives to homogeneous solution conditions that include dewetting of the π bond and an unsymmetrical perepoxide transition state in the hydroperoxide-forming step. The prenylsurfactants and a photoreactor technique allowed a certain degree of interfacial control of the hydroperoxidation reaction on a liquid support, where the oxidant (airborne ¹O₂) is delivered as a gas

S,S‐Chiral Linker Induced U Shape with a Syn‐facial Sensitizer and Photocleavable Ethene Group

There is a major need for light-activated materials for the release of sensitizers and drugs. Considering the success of chiral columns for the separation of enantiomer drugs, we synthesized an S,S-chiral linker system covalently attached to silica with a sensitizer ethene near the silica surface. First, the silica surface was modified to be aromatic rich, by replacing 70% of the surface groups with (3-phenoxypropyl)silane. We then synthesized a 3-component conjugate [chlorin sensitizer, S,S-chiral cyclohexane and ethene building blocks] in 5 steps with a 13% yield, and covalently bound the conjugate to the (3-phenoxypropyl)silane-coated silica surface. We hypothesized that the chiral linker would increase exposure of the ethene site for enhanced 1 O2-based sensitizer release. However, the chiral linker caused the sensitizer conjugate to adopt a U shape due to favored 1,2-diaxial substituent orientation; resulting in a reduced efficiency of surface loading. Further accentuating the U shape was p–p stacking between the (3-phenoxypropyl)silane and sensitizer. Semiempirical calculations and singlet oxygen luminescence data provided deeper insight into the sensitizer’s orientation and release. This study has lead to insight on modifications of surfaces for drug photorelease and can help lead to the development of miniaturized photodynamic devices.Fil: Ghosh, Goutam. City University of New York; Estados Unidos. Acadia University; CanadáFil: Belh, Sarah J.. City University of New York; Estados UnidosFil: Chiemezie, Callistus. City University of New York; Estados UnidosFil: Walalawela, Niluksha. City University of New York; Estados UnidosFil: Ghogare, Ashwini A.. City University of New York; Estados UnidosFil: Vignoni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Thomas, Andrés Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: McFarland, Sherri A.. Acadia University; Canadá. University of North Carolina; Estados UnidosFil: Greer, Edyta M.. City University of New York; Estados UnidosFil: Greer, Alexander. City University of New York; Estados Unido

Photoactive Fluoropolymer Surfaces That Release Sensitizer Drug Molecules

We describe a physical–organic study of two fluoropolymers bearing a photoreleasable PEGylated photosensitizer that generates ¹O₂(¹Δ_g) [chlorin e₆ methoxy tri­(ethylene glycol) triester]. The surfaces are Teflon/poly­(vinyl alcohol) (PVA) nanocomposite and fluorinated silica. The relative efficiency of these surfaces to photorelease the PEGylated sensitizer [shown previously to be phototoxic to ovarian cancer cells (Kimani, S. et al. <i>J. Org. Chem</i> <b>2012</b>, <i>77</i>, 10638)] was slightly higher for the nanocomposite. In the presence of red light and O₂, ¹O₂ is formed, which cleaves an ethene linkage to liberate the sensitizer in 68–92% yield. The fluoropolymers were designed to deal with multiple problems. Namely, their success relied not only on high O₂ solubility and drug repellency but also on the C–F bonds, which physically quench little ¹O₂, for singlet oxygen’s productive use away from the surface. The results obtained here indicate that Teflon-like surfaces have potential uses in delivering sensitizer and singlet oxygen for applications in tissue repair and photodynamic therapy (PDT)

Mechanism of Photochemical O‑Atom Exchange in Nitrosamines with Molecular Oxygen

The detection of an oxygen-atom photoexchange process of <i>N-</i>nitrosamines is reported. The photolysis of four nitrosamines (<i>N</i>-nitrosodiphenylamine <b>1</b>, <i>N</i>-nitroso-<i>N</i>-methylaniline <b>2</b>, <i>N</i>-butyl-<i>N</i>-(4-hydroxy­butyl)­nitrosamine <b>3</b>, and <i>N</i>-nitroso­diethylamine <b>4</b>) with ultraviolet light was examined in an ¹⁸O₂-enriched atmosphere in solution. HPLC/MS and HPLC-MS/MS data show that ¹⁸O-labeled nitrosamines were generated for <b>1</b> and <b>2</b>. In contrast, nitrosamines <b>3</b> and <b>4</b> do not exchange the ¹⁸O label and instead decomposed to amines and/or imines under the conditions. For <b>1</b> and <b>2</b>, the ¹⁸O atom was found not to be introduced by moisture or by singlet oxygen [¹⁸(¹O₂ ¹Δ_g)] produced thermally by ¹⁸O–¹⁸O labeled endoperoxide of <i>N,N</i>′-di­(2,3-hydroxy­propyl)-1,4-naphthalene dipropanamide (DHPN¹⁸O₂) or by visible-light sensitization. A density functional theory study of the structures and energetics of peroxy intermediates arising from reaction of nitrosamines with O₂ is also presented. A reversible head-to-tail dimerization of the <i>O-</i>nitrooxide to the 1,2,3,5,6,7-hexaoxa­diazocane (30 kcal/mol barrier) with extrusion of O¹⁸O accounts for exchange of the oxygen atom label. The unimolecular cyclization of <i>O-</i>nitrooxide to 1,2,3,4-trioxazetidine (46 kcal/mol barrier) followed by a retro [2 + 2] reaction is an alternative, but higher energy process. Both pathways would require the photoexcitation of the nitrooxide

Type I and Type II Photosensitized Oxidation Reactions : Guidelines and Mechanistic Pathways.

Here, 10 guidelines are presented for a standardized definition of type I and type II photosensitized oxidation reactions. Because of varied notions of reactions mediated by photosensitizers, a checklist of recommendations is provided for their definitions. Type I and type II photoreactions are oxygendependent and involve unstable species such as the initial formation of radical cation or neutral radicals from the substrates and/or singlet oxygen (1O2 1Δg) by energy transfer to molecular oxygen. In addition, superoxide anion radical (O2←) can be generated by a charge-transfer reaction involving O2 or more likely indirectly as the result of O2-mediated oxidation of the radical anion of type I photosensitizers. In subsequent reactions, O2← may add and/or reduce a few highly oxidizing radicals that arise from the deprotonation of the radical cations of key biological targets. O2← can also undergo dismutation into H2O2, the precursor of the highly reactive hydroxyl radical (OH) that may induce delayed oxidation reactions in cells. In the second part, several examples of type I and type II photosensitized oxidation reactions are provided to illustrate the complexity and the diversity of the degradation pathways of mostly relevant biomolecules upon one-electron oxidation and singlet oxygen reactions.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

Superhydrophobic Photosensitizers: Airborne ¹O₂ Killing of an in Vitro Oral Biofilm at the Plastron Interface

Singlet oxygen is a potent agent for the selective killing of a wide range of harmful cells; however, current delivery methods pose significant obstacles to its widespread use as a treatment agent. Limitations include the need for photosensitizer proximity to tissue because of the short (3.5 μs) lifetime of singlet oxygen in contact with water; the strong optical absorption of the photosensitizer, which limits the penetration depth; and hypoxic environments that restrict the concentration of available oxygen. In this article, we describe a novel superhydrophobic singlet oxygen delivery device for the selective inactivation of bacterial biofilms. The device addresses the current limitations by: immobilizing photosensitizer molecules onto inert silica particles; embedding the photosensitizer-containing particles into the plastron (i.e. the fluid-free space within a superhydrophobic surface between the solid substrate and fluid layer); distributing the particles along an optically transparent substrate such that they can be uniformly illuminated; enabling the penetration of oxygen via the contiguous vapor space defined by the plastron; and stabilizing the superhydrophobic state while avoiding the direct contact of the sensitizer to biomaterials. In this way, singlet oxygen generated on the sensitizer-containing particles can diffuse across the plastron and kill bacteria even deep within the hypoxic periodontal pockets. For the first time, we demonstrate complete biofilm inactivation (>5 log killing) of Porphyromonas gingivalis, a bacterium implicated in periodontal disease using the superhydrophobic singlet oxygen delivery device. The biofilms were cultured on hydroxyapatite disks and exposed to active and control surfaces to assess the killing efficiency as monitored by colony counting and confocal microscopy. Two sensitizer particle types, a silicon phthalocyanine sol–gel and a chlorin e6 derivative covalently bound to fluorinated silica, were evaluated; the biofilm killing efficiency was found to correlate with the amount of singlet oxygen detected in separate trapping studies. Finally, we discuss the applications of such devices in the treatment of periodontitis

Type I and Type II Photosensitized Oxidation Reactions: Guidelines and Mechanistic Pathways

Here, 10 guidelines are presented for a standardized definition of type I and type II photosensitized oxidation reactions. Because of varied notions of reactions mediated by photosensitizers, a checklist of recommendations is provided for their definitions. Type I and type II photoreactions are oxygen-dependent and involve unstable species such as the initial formation of radical cation or neutral radicals from the substrates and/or singlet oxygen (1O2 1∆g) by energy transfer to molecular oxygen. In addition, superoxide anion radical (O.- 2) can be generated by a charge-transfer reaction involving O2 or more likely indirectly as the result of O2-mediated oxidation of the radical anion of type I photosensitizers. In subsequent reactions, O.- 2 may add and/or reduce a few highly oxidizing radicals that arise from the deprotonation of the radical cations of key biological targets.O.- 2 can also undergo dismutation into H2O2, the precursor of the highly reactive hydroxyl radical (.OH) that may induce delayed oxidation reactions in cells. In the second part, several examples of type I and type II photosensitized oxidation reactions are provided to illustrate the complexity and the diversity of the degradation pathways of mostly relevant biomolecules upon one-electron oxidation and singlet oxygen reactions.Fil: Baptista, Maurício S.. Universidade de Sao Paulo; BrasilFil: Cadet, Jean. University of Sherbrooke; CanadáFil: Di Mascio, Paolo. Universidade de Sao Paulo; BrasilFil: Ghogare, Ashwini A.. Brooklyn College; Estados Unidos. City University of New York; Estados UnidosFil: Greer, Alexander. Brooklyn College; Estados Unidos. City University of New York; Estados UnidosFil: Hamblin, Michael R.. Massachusetts General Hospital; Estados Unidos. Harvard Medical School; Estados UnidosFil: Lorente, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Nunez, Silvia Cristina. Universidade Camilo Castelo Branco; BrasilFil: Simoes Ribeiro, Martha. Comissao Nacional de Energia Nuclear. Centro de Lasers e Aplicacoes. Instituto de Pesquisas Energeticas e Nucleares.; BrasilFil: Thomas, Andrés Héctor. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Vignoni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Yoshimura, Tania Mateus. Comissao Nacional de Energia Nuclear. Centro de Lasers e Aplicacoes. Instituto de Pesquisas Energeticas e Nucleares.; Brasi