Mild Irradiation Research Articles

Porphyrin Containing Polymersomes with Enhanced ROS Generation Efficiency: In Vitro Evaluation

Porphyrins are molecules possessing unique photophysical properties making them suitable for application in photodynamic therapy. The incorporation of porphyrins into natural or synthetic nano-assemblies such as polymersomes is a strategy to improve and prolong their therapeutic capacities and to overcome their limitations as therapeutic and diagnostic agents. Here, 5,10,15,20-tetrakis(1-(6-ethoxy-6-oxohexyl)-4-pyridin-1-io)-21H,23H-porphyrin tetrabromide porphyrin is inserted into polymersomes in order to demonstrate that the encapsulation enhances its ability to generate highly reactive singlet oxygen (1 O2 ) upon irradiation in vitro. The photoactivation of the free and polymersome-encapsulated porphyrin is evaluated by electron spin resonance and cell viability assays on three different mammalian cell lines. The results indicate that by encapsulating the porphyrin, a controlled ROS delivery within the cells is achieved, at the same time avoiding side effects such as dark toxicity, non-specific porphyrin release and over time decreased activity in vitro. This work focuses on showing a not-toxic model system for modern therapeutic nanomedicine, which works under mild irradiation and dosage conditions.

Bismuth embedded silica nanoparticles loaded with autophagy suppressant to promote photothermal therapy

An unpredicted side effect of photothermal therapy (PTT) is agitated by hyperthermia which results in damage to healthy tissue. Developing PTT platforms, enabling effective tumor ablation under mild irradiation conditions, is of wide interest, but challenging. Here, we investigated bismuth crystals embedded silica (Bi@SiO2) nanoparticles, loaded with an autophagy inhibitor (chloroquine, CQ). It was found that SiO2 effectively prevented the oxidization of Bi nanocrystals in the physiological environment and could serve as a scatter layer to improve NIR absorption, enabling a high photothermal conversion efficiency (~43%) and excellent photostability. Furthermore, the findings indicated that CQ molecules, delivered intracellularly by the particles, significantly weakened the degradation of autolysosomes by lysosome within the tumor cells, thus inducing suppression effect to autophagy and resistance to photothermia. Both in vitro and in vivo anti-tumor effects were consequently promoted owing to the combined effects enabled by Bi@SiO2-CQ nanoparticles under mild NIR irradiation conditions. This study demonstrates a potential new PTT platform with superior therapeutic efficacy.

Organic Photoredox-Catalyzed Synthesis of δ-Fluoromethylated Alcohols and Amines via 1,5-Hydrogen-Transfer Radical Relay

The hydrotrifluoromethylation of benzyl-protected homoallylic alcohol and amine derivatives catalyzed by 2,4,5,6-tetra(9 H-carbazol-9-yl)isophthalonitrile (4CzIPN) was developed. This reaction delivered δ-fluoromethylated free alcohols and amines with in situ deprotection of benzyl protecting group under mild irradiation conditions. 4CzIPN was found to be a competent metal-free photoredox catalyst for activating several types of fluoromethylation reagents including CF3SO2Cl, Togni's reagent, and 2-bromo-2,2-difluoroacetate via oxidative quenching and also CF3SO2Na through reductive quenching to allow direct hydrotrifluoromethylation of simple alkenes and Michael acceptors.

Simultaneous initiation of radical and cationic polymerization reactions using the “G1” copper complex as photoredox catalyst: Applications of free radical/cationic hybrid photopolymerization in the composites and 3D printing fields

This investigation presents the use of a photoredox catalyst "G1" as a photoinitiating system for free radical/cationic hybrid polymerization under mild irradiation conditions. The G1 system (G1/iodonium salt/N-vinylcarbazole), can simultaneously initiate the free radical and cationic polymerization reactions upon exposure to a visible (405 nm) light from a Light Emitting Diode (LED) source. The multicomponent G1 system is able to simultaneously generate radical and cationic species through a catalytic photoredox process. The curing of thin samples (25 μm), thick samples (1.4 mm) as well as the manufacture of hybrid system/glass fibers composites (˜2 to 4 mm thickness) was realized and the influence of the ratio of cationic/radical monomer blends on the polymerization kinetics was studied. The use of G1 in visible light photoinitiating system for the access to composites and 3D printing experiments was particularly outlined. G1 was also shown to have low levels of migration from the cured materials. When compared to reference materials ("F1", a similar copper complex and an anthracene derivative, dibutoxy anthracene), G1 showed better polymerization efficiency. The initiation efficiency was investigated through the real-time Fourier transform infrared (RT-FTIR) spectroscopy and optical pyrometry. Dynamical Mechanical Analysis has been used to determine the glass temperature transition of the cured hybrid system as a complementary technique.

Charge-Transfer Complexes as New Inhibitors/Photoinitiators for On-Demand Amine/Peroxide Redox Polymerization

Redox free-radical polymerizations have widespread applications but still clearly suffer from poor time control of the reaction. Currently, the workability (delay of the gel time) in redox polymerization after mixing is possible thanks to two main types of inhibitors (radical scavengers): phenols and nitroxides. Out of this trend, we propose in this work an alternative strategy for time delaying of the redox polymerization, which is based on charge-transfer complexes (CTCs). Thanks to iodonium salt complexation, the amine (here 4-N,N-trimethylaniline) is proposed to be stored in a CTC equilibrium and is slowly released over a period of time (as a result of the consumption of free amines by peroxides). This alternative strategy allowed us to double the gel time (e.g., from 60 to 120 s) while maintaining a high polymerization efficiency (performance comparable to reference nitroxides). More interestingly, the CTCs involved in this retarding strategy are photoresponsive under visible LED@405 nm and can be used on demand as photoinitiators, allowing (i) spectacular increases in polymerization efficiencies (from 50 °C without light to 120 °C under mild irradiation conditions); (ii) drastic reduction of the oxygen-inhibited layer (already 45% C=C conversion at a 2 μm distance from the top surface) compared to the nonirradiated sample (thick inhibited layer of more than 45 μm); and (iii) external control of the redox polymerization gel time due to the possible light activation.

Metal Acetylacetonate–Bidentate Ligand Interaction (MABLI) (Photo)activated Polymerization: Toward High Performance Amine-Free, Peroxide-Free Redox Radical (Photo)initiating Systems

Free radical polymerization (FRP) initiation from metal acetylacetonate–bidentate ligand interaction (MABLI) under mild conditions (room temperature, under air) is discussed here for different metal centers (Mn, V, and Cu). First, without light, in MABLI systems such as V(acac)3/2-diphenylphosphinobenzoic acid (2dppba), Mn(acac)3/2dppba, or Cu(acac)2/2dppba, electron-rich aryl (Ar•) radicals were conveniently and efficiently produced by the reaction of electron-poor acac• radicals with the iodonium salt (Iod), leading to an enhancement of pure redox (no light) polymerizations. Second, it was found that V(III)*/Iod reaction is generating aryl (Ar•) radicals at a high enough rate to initiate a photopolymerization process upon mild irradiation (LED@405 nm). This reaction can be implemented in redox photoactivated systems (e.g., using three-component V(acac)3/2dppba/Iod systems) in order to spectacularly enhance a slow redox process from 40 °C exothermicity in 800 s to 93 °C in less than 200 s. Third, an impr...

Wavelength-Selective Coupling and Decoupling of Polymer Chains via Reversible [2 + 2] Photocycloaddition of Styrylpyrene for Construction of Cytocompatible Photodynamic Hydrogels.

Reversible photocycloaddition reactions have previously been employed in chemical cross-linking for the preparation of biomaterial scaffolds. However, the processes require activation by high-energy UV light, rendering them unsuitable for modification in biological environments. Here we demonstrate that the [2 + 2] photocycloaddition of styrylpyrene can be activated by visible light at λ = 400-500 nm, enabling rapid and effective conjugation and cross-linking of poly(ethylene glycol) (PEG) in water and under mild irradiation conditions (I = 20 mW cm-2). Notably, the reversion of the cycloaddition can be triggered by low-energy UV light at λ = 340 nm, which allows for efficient cleavage of the dimer adduct. Using this wavelength-gated reversible photochemical reaction we are able to prepare PEG hydrogels and modulate their mechanical properties in a bidirectional manner. We also demonstrate healing of the fractured hydrogel by external light triggers. Furthermore, we show that human mesenchymal stem cells can be encapsulated within the gels with high viability post encapsulation. This photochemical approach is therefore anticipated to be highly useful in studies of cell mechanotransduction, with relevance to disease progression and tissue regeneration.

Photo Irradiation-Induced Core Crosslinked Poly(ethylene glycol)-block-poly(aspartic acid) Micelles: Optimization of Block Copolymer Synthesis and Characterization of Core Crosslinked Micelles.

We used photo irradiation to design core crosslinked polymeric micelles whose only significant physico-chemical change was in their physico-chemical stability, which helps elucidate poly(ethylene glycol) (PEG)-related immunogenicity. Synthetic routes and compositions of PEG-b-poly(aspartic acid) block copolymers were optimized with the control of n-alkyl chain length and photo-sensitive chalcone moieties. The conjugation ratio between n-alkyl chain and the chalcone moieties was controlled, and upon the mild photo irradiation of polymeric micelles, permanent crosslink proceeded in the micelle cores. In the optimized condition, the core crosslinked (CCL) micelles exhibited no dissociation while the non-CCL micelles exhibited dissociation. These results indicate that the photo-crosslinking reactions in the inner core were successful. A gel-permeation chromatography (GPC) measurement revealed a difference between the micellar-formation stability of CCL micelles and that of the non-CCL micelles. GPC experiments revealed that the CCL micelles were more stable than the non-CCL micelles. Our research also revealed that photo-crosslinking reactions did not change the core property for drug encapsulation. In conclusion, the prepared CCL micelles exhibited the same diameter, the same formula, and the same inner-core properties for drug encapsulation as did the non-CCL micelles. Moreover, the CCL micelles exhibited non-dissociable micelle formation, while the non-CCL micelles exhibited dissociation into single block copolymers.

Novel Carbazole Skeleton-Based Photoinitiators for LED Polymerization and LED Projector 3D Printing.

Radical chemistry is a very convenient way to produce polymer materials. Here, an application of a particular photoinduced radical chemistry is illustrated. Seven new carbazole derivatives Cd1–Cd7 are incorporated and proposed as high performance near-UV photoinitiators for both the free radical polymerization (FRP) of (meth)acrylates and the cationic polymerization (CP) of epoxides utilizing Light Emitting Diodes LEDs @405 nm. Excellent polymerization-initiating abilities are found and high final reactive function conversions are obtained. Interestingly, these new derivatives display much better near-UV polymerization-initiating abilities compared to a reference UV absorbing carbazole (CARET 9H-carbazole-9-ethanol) demonstrating that the new substituents have good ability to red shift the absorption of the proposed photoinitiators. All the more strikingly, in combination with iodonium salt, Cd1–Cd7 are likewise preferred as cationic photoinitiators over the notable photoinitiator bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (BAPO) for mild irradiation conditions featuring their remarkable reactivity. In particular their utilization in the preparation of new cationic resins for LED projector 3D printing is envisioned. A full picture of the included photochemical mechanisms is given.

Carbazole Scaffold Based Photoinitiator/Photoredox Catalysts: Toward New High Performance Photoinitiating Systems and Application in LED Projector 3D Printing Resins

Four new carbazole derivatives (C1–C4) are synthesized and proposed as high performance visible light photoinitiators/photoredox catalysts for both the free radical polymerization (FRP) of (meth)acrylates and the cationic polymerization (CP) of epoxides upon visible light exposure using light-emitting diodes (LEDs) at 405, 455, and 477 nm. Excellent polymerization initiating abilities are found, and high final reactive function conversions are obtained. Interestingly, these new derivatives exhibit much better visible light polymerization initiating ability compared to a reference UV-absorbing carbazole (CARET, 9H-carbazole-9-ethanol) showing that the new substituents are of great interest to red-shift the absorption of the proposed photoinitiators. More remarkably, in combination with an iodonium salt, C1–C4 are also better than the well-known bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (BAPO) photoinitiator for mild irradiation conditions highlighting their outstanding reactivity. Their use in new c...

Photochemical functionalization of diazines: metal-free vinylation and phosphonylation

Under mild UVA irradiation, the CBr bond of bromodiazines can be activated to generate the corresponding radical intermediate. In the presence of alkynes, alkenylation reactions occurred to afford vinyl pyrimidine in moderate yields. Csp2-phosphorous bond can also be easily created in a photochemical version of the Arbuzov reaction. With UVA and a stoichiometric amount of trimethyl phosphite, the corresponding phosphonates were isolated in good to high yields. Very interesting selectivities were observed under these mild irradiation conditions. Functionalized substrates can be engaged and the resulting products could be further derivatized.

Synthesis of a Novel Quinoline Skeleton Introduced Cationic Polyfluorene Derivative for Multimodal Antimicrobial Application.

A new functional polyfluorene derivative containing quinoline skeleton and quarternary ammonium group (QAG) modified side chains (PFPQ) was synthesized and characterized. The multimodal antimicrobial effect toward Gram-negative E. coli was achieved by the dark toxicity resulting from the quinoline skeleton, QAG, and light toxicity resulting from reactive oxygen species (ROS) produced by the main backbone of PFPQ under white light. The mechanism of interaction between PFPQ and bacteria was also demonstrated. PFPQ bound to E. coli mainly through electrostatic interactions causing nearly 50% bacterial death in the absence of light irradiation, and the huge capability of PFPQ to generate ROS under white light opened another bactericidal mode. The killing efficiency was more than 99% upon relatively mild irradiation under white light (400-800 nm) with a light dose of 18 J·cm(-2). PFPQ with the incorporation of quinoline into the backbones will provide a new versatile strategy to achieve the multimodal antimicrobial effect to fight against resistant bacteria.

Effect of the positional isomerism on the photoreactivity of styryloxazoles

Abstract This paper describes the results obtained in the study of the photobehaviour of heteroanalogs of stilbene bearing an oxazole ring. The competitive relaxation processes (fluorescence, isomerization and cyclization) of the excited states of n-styryloxazoles (n = 2 and 4) were investigated and compared with the behaviour previously reported for n = 5. After preparation of the unknown compound with n = 4 and of its positional isomer with n = 2 (the latter with a new method of synthesis), their photobehaviour was firstly investigated in preparative conditions by NMR analysis to measure the chemical yields of their photoproducts. The study was then continued in mild irradiation conditions to measure the quantum yields of the competitive photoreactions in the primary irradiation steps. The effects of the position of the styryl group at the oxazole ring, the relative abundance of the various conformers and the possible formation of intramolecular H bonds on the deactivation pathways are described. Quantum-mechanical Hyperchem calculations proved to be very useful to describe the conformational equilibria and the role of conformers on photoreactivity while more refined DFT calculations on the Z isomers allowed to explain the structure dependent competition between their isomerization/cyclization processes. The effect of the replacement of the phenyl ring with a second heteroaromatic group of electron donor character was investigated for the 5-(2-(furan-2-yl) ethenyl) oxazole.

Multiscale patterning of graphene oxide and reduced graphene oxide for flexible supercapacitors

A simple and facile method for multiscale, in-plane patterning of graphene oxide and reduced graphene oxide (GO–rGO) was developed by region-specific reduction of graphene oxide (GO) under a mild irradiation. The UV-induced reduction of graphene oxide was monitored by various spectroscopic techniques, including optical absorption, X-ray photoelectron spectroscopy (XPS), Raman, and X-ray diffraction (XRD), while the resultant GO–rGO patterned film morphology was studied on optical microscope, scanning electron microscope (SEM), and atomic force microscope (AFM). Flexible symmetric and in-plane supercapacitors were fabricated from the GO–rGO patterned polyethylene terephthalate (PET) electrodes to show capacitances up to 141.2F/g.

Axially paraben substituted silicon(IV) phthalocyanines towards dental pathogen Streptococcus mutans: Synthesis, photophysical, photochemical and in vitro properties

A series of silicon(IV) phthalocyanines axially substituted with methylparaben, ethylparaben, propylparaben and butylparaben groups were synthesized and studied as photosensitizers for antimicrobial photodynamic therapy. The absorption, fluorescence, photodegradation and singlet oxygen generation properties of the synthesized Si(IV) phthalocyanines were studied. In vitro antibacterial photodynamic therapy was investigated against cariogenic pathogenic bacterium Streptococcus mutans. Axially propylparaben substituted Si(IV) phthalocyanine showed significant photodynamic efficacy (log 4) at concentration of 10 μM and mild irradiation (60 mW cm−2, 50 J cm−2, LED 637 nm). The low inactivation capacity was observed for the other studied Si(IV) phthalocyanines. The uptake and localization properties of axially propylparaben substituted Si(IV) phthalocyanine showed a sufficient level of accumulation in planktonic cultured bacterium and a complete penetration depth into the biomass of the 48-h bacterial biofilm.

A novel strategy of radiofrequency hyperthermia (neothermia) in combination with preoperative chemoradiotherapy for the treatment of advanced rectal cancer: a pilot study.

The safety of weekly regional hyperthermia performed with 8 MHz radiofrequency (RF) capacitive heating equipment has been established in rectal cancer. We aimed to standardize hyperthermia treatment for scientific evaluation and for assessing local tumor response to RF hyperthermia in rectal cancer. Forty-nine patients diagnosed with rectal adenocarcinoma were included in the study. All patients received chemoradiation with intensity-modulated radiation therapy 5 days/week (dose, 50 Gy/25 times) concomitant with 5 days/week for five times of capecitabine (1700 mg/m2 per day) and once a week for five times of 50 min irradiations by an 8 MHz RF capacitive heating device. Thirty-three patients underwent surgery 8 weeks after treatment. Three patients did not undergo surgery because of progressive disease (PD) and 13 refused. Eight (16.3%) patients had a pathological complete response (ypCR) after surgery. Among patients without surgery, 3 (6.1%) had clinical complete response (CR) and 3 (6.1%) had local CR but distant PD (CRPD). Ninety percent of ypCR + CR patients were shown in 6.21 W min−1 m−2/treatment or higher group of average total accumulated irradiation output with 429°C min−1 m−2 or higher group of total accumulated thermal output. However, a patient with CRPD was in the higher total accumulated thermal output group. We propose a new quantitative parameter for the hyperthermia and demonstrated that patients can benefit from mild irradiation with mild temperature. Using these parameters, the exact output, optimal thermal treatment, and contraindications or indications of this modality could be determined in a multi-institutional, future study.

Kinetics of ultrasound-assisted enzymatic biodiesel production from Macauba coconut oil

This work reports the production of fatty acid ethyl esters (FAEE) by means of Macauba (Acrocomia aculeata) coconut oil (MCO) solvent-free enzymatic transesterification reactions using a commercial immobilized lipase (Novozym 435) under the influence of ultrasound irradiation. An experimental design was used to evaluate the effects of temperature (40–70 °C), enzyme (5–20 wt%) concentration, oil to ethanol molar ratio (1:3–1:10) and output irradiation power (40–70 % of the maximum supply value) on the reaction yield. Besides, a kinetic study varying the enzyme concentration was also carried out. Results show that ultrasound-assisted lipase-catalyzed transesterification of MCO with ethanol in solvent-free system might be a potential alternative route to conventional alkali-catalyzed and/or traditional enzymatic methods, as reaction yields around 70 wt% were obtained at mild irradiation power supply (∼ 132 W), and temperature (65 °C) in a short reaction time, 30 min. Reutilization of enzyme showed that it may be advantageously employed up to 5 reuse cycles.

Enzyme-catalyzed production of biodiesel by ultrasound-assisted ethanolysis of soybean oil in solvent-free system.

This work reports the transesterification of soybean oil with ethanol using a commercial immobilized lipase, Novozym 435, under the influence of ultrasound irradiation, in a solvent-free s. The experiments were performed in an ultrasonic water bath, following a sequence of experimental designs to evaluate the effects of temperature, enzyme and water concentrations, oil to ethanol molar ratio and output irradiation power on the reaction yield. Besides, a kinetic study varying the substrates molar ratio and enzyme concentration was also carried out. Results show that ultrasound-assisted lipase-catalyzed transesterification of soybean oil with ethanol in solvent-free system might be a potential alternative route to conventional alkali-catalyzed and/or traditional enzymatic methods, as high reaction yields (~78wt%) were obtained at mild irradiation power supply (~132W), and temperature (63°C) in a relatively short reaction time, 1h. Additionally, a study regarding the enzyme reuse was carried out at the experimental condition that afforded the best reaction yield.

Chemical Reactions Triggered Using Electrons Photodetached from "Clean" Distributions of Anions Deposited in Cryogenic Matrices via Counterion Codeposition.

Application of matrix isolation spectroscopy to ionic species is typically complicated by the presence of neutral contaminants during matrix deposition. Herein we demonstrate that simultaneous deposition of balanced currents of counterions with mass-selected ions of interest generates "clean" distributions of matrix-isolated metal carbonyl anions, where the only bands appearing in the CO-stretching region of the vibrational spectrum arise from ions. (Neutrals are initially absent.) Photodetachment by mild irradiation with visible light leads to complete conversion of the anions into their corresponding neutral species. The photodetached electrons, in turn, initiate covalent chemistry, inducing C-C bond formation following electron-capture by CO van der Waals dimers to produce trans-OCCO(-). The initial clean distribution of ions enables clear connections to be drawn between the spectral changes occurring at each experimental step, thus demonstrating the potential of the counterion codeposition technique to facilitate detailed studies of chemistry involving ions and electron transfer in cryogenic matrices.

Photic injury to cultured RPE varies among individual cells in proportion to their endogenous lipofuscin content as modulated by their melanosome content.

We determined whether photic stress differentially impairs organelle motility of RPE lipofuscin and melanin granules, whether lethal photic stress kills cells in proportion to lipofuscin abundance, and whether killing is modulated by melanosome content. Motility of endogenous lipofuscin and melanosome granules within the same human RPE cells in primary culture was quantified by real-time imaging during sublethal blue light irradiation. Cell death during lethal irradiation was quantified by dynamic imaging of the onset of nuclear propidium iodide fluorescence. Analyzed were individual cells containing different amounts of autofluorescent lipofuscin, or similar amounts of lipofuscin and a varying content of phagocytized porcine melanosomes, or phagocytized black latex beads (control for light absorbance). Lipofuscin granules and melanosomes showed motility slowing with mild irradiation, but slowing was greater for lipofuscin. On lethal irradiation, cell death was earlier in cells with higher lipofuscin content, but delayed by the copresence of melanosomes. Delayed death did not occur with black beads, suggesting that melanosome protection was due to properties of the biological granule, not simple screening. Greater organelle motility slowing of the more photoreactive lipofuscin granule compared to melanosomes suggests that lipofuscin mediates mild photic injury within RPE cells. With lethal light stress endogenous lipofuscin mediates killing, but the effect is cell autonomous and modulated by coincident melanosome content. Developing methods to quantify the frequency of individual cells with combined high lipofuscin and low melanosome content may have value for predicting the photic stress susceptibility of the RPE monolayer in situ.