Enhanced Singlet Oxygen Production Research Articles

Carcinomembrane-Camouflaged Perfluorochemical Dual-Layer Nanopolymersomes Bearing Indocyanine Green and Camptothecin Effectuate Targeting Photochemotherapy of Cancer.

Photochemotherapy has been recognized as a promising combinational modality for cancer treatment. However, difficulties such as off-target drug delivery, systemic toxicity, and the hypoxic nature of the tumor microenvironment remain hindrances to its application. To overcome these challenges, cancer cell membrane camouflaged perfluorooctyl bromide (PFOB) dual-layer nanopolymersomes bearing indocyanine green (ICG) and camptothecin (CPT), named MICFNS, were developed in this study, and melanoma was exploited as the model for MICFNS manufacture and therapeutic application. Our data showed that MICFNS were able to stabilize both ICG and CPT in the nanocarriers and can be quickly internalized by B16F10 cells due to melanoma membrane-mediated homology. Upon NIR irradiation, MICFNS can trigger hyperthermia and offer enhanced singlet oxygen production due to the incorporation of PFOB. With ≥10/2.5 μM ICG/CPT, MICFNS + NIR can provide comparable in vitro cancericidal effects to those caused by using an 8-fold higher dose of encapsulated CPT alone. Through the animal study, we further demonstrated that MICFNS can be quickly brought to tumors and have a longer retention time than those of free agents in vivo. Moreover, the MICFNS with 40/10 μM ICG/CPT in combination with 30 s NIR irradiation can successfully inhibit tumor growth without systemic toxicity in mice within the 14 day treatment. We speculate that such an antitumoral effect was achieved by phototherapy followed by chemotherapy, a two-stage tumoricidal process performed by MICFNS. Taken together, we anticipate that MICFNS, a photochemotherapeutic nanoplatform, has high potential for use in clinical anticancer treatment.

The role of efflux pump inhibitor in enhancing antimicrobial efficiency of Ag NPs and MB as an effective photodynamic therapy agent

Efflux pumps are active transporters, which allow the cell to remove toxic substances from within the cell including antibiotics and photosensitizer complexes. Efflux pump inhibitors (EPIs), chemicals that prevent the passage of molecules through efflux pumps, play a crucial role in antimicrobial effectiveness against pathogen. In this work, we studied the effect of EPI, namely, reserpine, on photodeactivation rate of pathogens when used with Ag NPs and methylene blue (MB). Our results show that using reserpine led to a higher deactivation rate than Ag NPs and MB alone. The mechanism of this observation was investigated with singlet oxygen generation amount. Additionally, different sizes of Ag NPs were tested with reserpine. Molecular docking calculation shows that reserpine had higher affinity toward AcrB than MB. The improvement in bacterial deactivation rate is attributed to blockage of the AcrAB-TolC efflux pump preventing the removal of MB rather than enhanced singlet oxygen production. These results suggest that using reserpine with nanoparticles and photosynthesize is a promising approach in photodynamic therapy.

Ionized water-soluble organic nanosheets with light/ultrasound dual excitation channels for efficient killing of multidrug-resistant bacteria.

A novel ionized heavy-atom-free two-dimensional organic nanosheet was prepared and exhibited highly selective generation of singlet oxygen under both light and ultrasound excitation. These ionized nanosheets displayed excellent dispersibility in water and enhanced singlet oxygen production efficiency compared to their non-assembled monomers. Antimicrobial experiments have revealed their potent bactericidal effects on drug-resistant E. coli and S. aureus under both visible light and ultrasound irradiation.

Enhanced singlet oxygen production under nanoconfinement using silica nanocomposites towards improving the photooxygenation’s conversion

Enhanced singlet oxygen production under nanoconfinement using silica nanocomposites towards improving the photooxygenation’s conversion

Photosensitizer Encryption with Aggregation Enhanced Singlet Oxygen Production.

Chromophores that generate singlet oxygen (1O2) in water are essential to developing noninvasive disease treatments using photodynamic therapy (PDT). A facile approach for formation of stable colloidal nanoparticles of 1O2 photosensitizers, which exhibit aggregation enhanced 1O2 generation in water toward applications as PDT agents, is reported. Chromophore encryption within a fuchsonarene macrocyclic scaffold insulates the photosensitizer from aggregation induced deactivation pathways, enabling a higher chromophore density than typical 1O2 generating nanoparticles. Aggregation enhanced 1O2 generation in water is observed, and variation in molecular structure allows for regulation of the physical properties of the nanoparticles which ultimately affects the 1O2 generation. In vitro activity and the ability of the particles to pass through the cell membrane into the cytoplasm is demonstrated using confocal fluorescence microscopy with HeLa cells. Photosensitizer encryption in rigid macrocycles, such as fuchsonarenes, offers new prospects for the production of biocompatible nanoarchitectures for applications involving 1O2 generation.

Synthesis of a near infrared-actuated phthalocyanine-lipid vesicle system for augmented photodynamic therapy

The efficacy of photodynamic therapy (PDT) is often limited by the poor bio-distributive properties of conventional photosensitizers and the local hypoxic microenvironment that characterises most solid tumours. Herein, a novel in situ oxygenic lipid formulation for photodynamic therapy (PDT) is reported. Such a hybrid was synthesized by adsorbing bimetallic nanozyme, MnO2@PtNPs (NPs = nanoparticles) onto graphene quantum dots (GQDs) – zinc (II) phthalocyanine conjugates, followed by liposomal encapsulation, affording it enhanced water solubility. The MnO2@PtNPs, which are is shown to possess excellent catalase-like properties surpassing that of MnO2 or PtNPs alone, serves to catalyze H2O2 to O2, while the zinc (II) phthalocyanine (1) serves to transform the formed oxygen to generate cytotoxic singlet oxygen immediately. We show that by combining each function of the respective building blocks, the as-synthesized 1-GQDs-MnO2@PtNPs-liposomes not only maintains the properties of oxygen supplementation through H2O2 catalysis but also displays cooperative properties for enhanced singlet oxygen production. Consequently, a remarkably improved PDT efficacy was observed for 1-GQDs-MnO2@PtNPs-liposomes in both normoxia and hypoxia. These results demonstrate the potential applicability of such nanozyme constituted 1-GQDs-MnO2@PtNPs-liposomes for achieving tumour treatment in hypoxic conditions by PDT.

Enhanced singlet oxygen production over a photocatalytic stable metal organic framework composed of porphyrin and Ag

Porphyrin is an important photosensitizer for singlet oxygen (1O2) formation. However, porphyrin derivatives still display low efficiency and difficult recovery. In this work, an Ag-based MOFs (AgTPyP; TPyP, 5,10,15,20-tetra(4-pyridyl) porphyrin) is synthesized. Compared with ligand TPyP, AgTPyP shows nearly 100% conversion and selectivity in the photocatalytic selective oxidation of sulfides to sulfoxides and obvious photodynamic therapeutic effect under visible light. Combined characterizations suggest that 1O2 is the only active oxygen species, which is due to the large exciton binding energy and narrow energy gap between the lowest excited singlet state (S1) and the lowest triplet state (T1) induced by the presence of Ag+ ion. The selectivity and conversion efficiency of five-cycle experiments do not decrease, indicating the excellent stability of AgTPyP. This work provides an alternative approach to simultaneously enhance the exciton effect of porphyrin and stabilize Ag-based photocatalysts.

Engineering BiOBrxI1−x solid solutions with enhanced singlet oxygen production for photocatalytic benzylic C[sbnd]H bond activation mediated by N-hydroxyl compounds

The aerobic, selective oxidation of hydrocarbons via CH bond activation is still a challenge. This work shows the achievement of the room temperature visible light driven photocatalytic activation of benzylic CH bonds with N-hydroxysuccinimide over BiOBrxI1-x (0 ≤ x ≤ 1) solid solutions, whose valance bands were engineered through varying the ratio of bromide to iodide. The optimal BiOBr0.85I0.15 catalyst exhibited over 98% conversion ratio of ethylbenzene, which was about 3.9 and 8.9 times that of pure BiOBr and BiOI, respectively. The excellent photocatalytic activity of BiOBr0.85I0.15 solid solution can be ascribed to the orbital hybridization of the valence band containing both Br 4p and I 5p orbitals, which could promote photo-induced charge carrier separation and improve the generation of singlet oxygen. This work shed some light on the rational design of photocatalysts for targeted organic transformation.

Stable Twisted Conformation Aza-BODIPY NIR-II Fluorescent Nanoparticles with Ultra-Large Stokes Shift for Imaging-Guided Phototherapy

Fluorescence imaging in the second near-infrared window (NIR-II, 1000–1700 nm) holds great promise for in vivo imaging and imaging-guided phototherapy with deep penetration and high spatiotemporal resolution. It is very appealing to obtain NIR-II fluorescent probes through simple procedures and economical substrates. Herein, we developed a D-A-D structure NIR-II photosensitizer (Triphenylamine modified Aza-Bodipy, TAB) based on the strong electron-withdrawing nature of borane difluoride azadipyrromethene’s center(aza-BODIPY). Subsequently, halogen atoms (Br, I) are introduced to the TAB molecule, TAB-2Br and TAB-2I were synthesized. DFT calculations demonstrated the twisted conformations of the TABs, which would effectively prevent π–π stacking in the aggregate state, to restrain the aggregation-caused quenching (ACQ). Compared to the TAB molecule, significant redshifts in emission wavelength, ultra-large Stokes shift (>360 nm), and enhanced singlet oxygen production capacity were acquired for the halogenated molecules. After encapsulated by an amphiphilic polypeptide POEGMA 23-PAsp20 there formed nanoparticles via self-assembly, and the obtained P-TAB, P-TAB-2Br and P-TAB-2I nanoparticles possessed excellent water solubility and biocompatibility, remarkable photothermal conversion efficiency (beyond 40%), good resistance to photobleaching, heat, and H2O2. Under 808 nm laser irradiation, the P-TAB-2Br exhibited efficient NIR-II fluorescence emission, and the abdominal vessel of the mouse could be clearly distinguished from the surrounding background tissue. In vitro and in vivo experiments revealed that P-TABs display excellent cell lethality and tumor ablation results under 808 nm irradiation. All of these results make the TABs potential organic probes for clinical NIR-II fluorescence imaging and cancer phototherapy.

Simultaneous Increase in Brightness and Singlet Oxygen Generation of an Organic Photosensitizer by Nanocrystallization.

Efficient organic photosensitizers are attractive for cancer cell ablation in photodynamic therapy. Bright fluorescent photosensitizers are highly desirable for simultaneous imaging and therapy. However, due to fundamental competition between emission and singlet oxygen generation, design attempts to increase singlet oxygen generation almost always leads to the loss of fluorescence. Herein, it is shown for the first time that nanocrystallization enables a simultaneous and significant increase in the brightness and singlet oxygen generation of an organic photosensitizer. Spectroscopic studies show simultaneous enhancement in the visible light absorption and fluorescence after nanocrystallization. The enhanced absorption of visible light in nanocrystals is found to translate directly to the enhanced singlet oxygen production, which shows a higher ability to kill HeLa cells as compared to their amorphous counterpart.

Self-Assembled Rose Bengal-Exopolysaccharide Nanoparticles for Improved Photodynamic Inactivation of Bacteria by Enhancing Singlet Oxygen Generation Directly in the Solution.

It is of great value to develop new antibacterial photodynamic therapy (PDT) strategies to improve antibacterial PDT efficacy of noncationic photosensitizers without introducing cytotoxicity, which is a great challenge for current leading efforts on antimicrobial PDT based on cell surface engineering. In this research, the hydrophobic and anionic photosensitizer rose bengal (RB) was chemically conjugated with bacterial exopolysaccharide (EPS) to generate an amphiphilic and negatively charged compound EPS-RB that could self-assemble into nanoparticles (NPs) in solution. These EPS-RB NPs possessed an increased singlet oxygen generation property in solution. As a result, EPS-RB exhibited improved photoinactivation for both Gram-negative and Gram-positive bacteria, leading to a record low RB working concentration, 8 μM or 500 nM for Escherichia coli or Staphylococcus aureus, respectively. Upon light irradiation, more EPS-RB bound to the cell surface and penetrated into bacteria than RB, with EPS-RB staying around the cell surface of the most irradiated E. coli while entering all irradiated S. aureus. Both scanning electron microscopy and fluorescence confocal imaging results show that the cell membrane of E. coli was damaged heavily but not S. aureus. All of these observations indicate that both the enhanced singlet oxygen production of EPS-RB NPs in solution and their consequently increased membrane binding and cellular penetration into the bacteria through the damaged cell membrane contribute to their significantly improved bacterial photoinactivation efficiency. In addition, EPS-RB has low cytotoxicity and negligible hemolytic activity, showing great biocompatibility. Therefore, the construction of EPS-RB provides a new strategy for the PDT effectiveness improvement of the separated cell/sensitizer systems and thus the design of next-generation antimicrobial agents.

Postsynthetic Incorporation of a Singlet Oxygen Photosensitizer in a Metal-Organic Framework for Fast and Selective Oxidative Detoxification of Sulfur Mustard.

A fullerene-based photosensitizer is incorporated postsynthetically into a Zr6 -based MOF, NU-1000, for enhanced singlet oxygen production. The structural organic linkers in the MOF platform also act as photosensitizers which contribute to the overall generation of singlet oxygen from the material under UV irradiation. The singlet oxygen generated by the MOF/fullerene material is shown to oxidize sulfur mustard selectively to the less toxic bis(2-chloroethyl)sulfoxide with a half-life of only 11 min.

CdSe/ZnS Core/Shell Quantum Dots in Cooperation with Other Materials for Direct and Indirect Production of Reactive Oxygen Species.

In this present work, CdSe/ZnS core/shell quantum dots (QDs) were exploited in the oxidation reactions of 5-aminolevulinic acid (ALA) and glutamate (GLU) for the production of reactive oxygen species (ROS). Fast and highly efficient oxidation reactions of ALA to produce the hydroxyl radicals (HO*) and of GLU to produce the superoxide anion (O2*-) were observed in the cooperation of mercaptopropionic acid (MPA) capped-CdSe/ZnS QDs (MPA-QDs) under LED irradiation. Whereas, binding between MPA-QDs and coumarin-derived dendrimer (CdD)-captured silica particles (SiCdDs) through sol-gel GA enhanced singlet oxygen production under LED irradiation by about 80% as compared to that achieved using QDs only. Confocal fluorescent microscopic images of the size and morphology of HeLa cells confirmed the ROS production from ALA, GLU in cooperation with CdSe/ZnS QDs or QDs-coated SiCdDs under LED irradiation.

Enhanced singlet oxygen production by photodynamic therapy and a novel method for its intracellular measurement.

The generation of singlet oxygen (SO) in the presence of specific photosensitizers (PSs) or semiconductor quantum dots (QDs) and its application in photodynamic therapy (PDT) is of great interest to develop cancer therapies with no need of surgery, chemotherapy, and/or radiotherapy. This work was focused on the identification of the main factors leading to the enhancement of SO production using Rose Bengal (RB), and Methylene Blue (MB) as PS species in organic and aqueous mediums. Subsequently, the capacity of zinc oxide (ZnO), zinc sulfide (ZnS), and ZnO/ZnS core-shell QDs as well as manganese (Mn(+2)) doped ZnO and ZnS nanoparticles (NPs) as potential PS was also investigated. Many variable parameters such as type of quencher, PSs, NPs, as well as its different concentrations, light source, excitation wavelength, reaction time, distance from light source, and nature of solvent were used. The degradation kinetics of the quenchers generated by SO species and the corresponding quantum yields were determined by monitoring the photo-oxidation of the chemical quencher and measuring its disappearance by fluorometry and spectrophotometry in the presence of NPs. Small intracellular changes of SO induced by these metal Zn (zinc) NPs and PDT could execute and accelerate deadly programs in these leukemic cells, providing in this way an innovative modality of treatment. In order to perform further more specific in vitro cytotoxic studies on B-chronic lymphocytic leukemia cells exposed to Zn NPs and PDT, we needed first to measure and ascertain those possible intracellular SO variations generated by this type of treatment; for this purpose, we have also developed and tested a novel method first described by us.

Surface plasmon-photosensitizer resonance coupling: an enhanced singlet oxygen production platform for broad-spectrum photodynamic inactivation of bacteria.

Singlet oxygen plays a critical role in a great number of applications including photodynamic therapy of cancers, photodynamic inactivation of microorganisms, photooxidation, and photodegradation of polymers. Herein we demonstrate a general platform to improve singlet oxygen production via resonance coupling between surface plasmon and photosensitizers. By loading photosensitizers into mesoporous silica containing silver nanoparticles, strong resonance coupling between the photosensitizers and the silver core markedly increases the singlet oxygen production, by up to three orders of magnitude in some cases. It is observed that the more spectral overlap between the surface plasmon resonance spectrum of the silver core and the photosensitizers' absorption spectra, the greater the singlet oxygen production. The as-synthesized hybrids have shown exceptionally high photoinactivation efficiency against both Gram-positive and Gram-negative bacteria. This work establishes a general platform to improve singlet oxygen production and to develop more effective and efficient hybrid photosensitizers for broad-spectrum photodynamic inactivation of bacteria.

Singlet Oxygen Scavenging Activity and Cytotoxicity of Essential Oils from Rutaceae

Since we have been exposed to excessive amounts of stressors, aromatherapy for the relaxation has recently become very popular recently. However, there is a problem which responds to light with the essential oil used by aromatherapy. It is generally believed that singlet oxygen is implicated in the pathogenesis of various diseases such as light-induced skin disorders and inflammatory responses. Here we studied whether essential oils can effectively scavenge singlet oxygen upon irradiation, using the electron spin resonance (ESR) method. Green light was used to irradiate twelve essential oils from rutaceae. Among these twelve essential oils, eight were prepared by the expression (or the compression) method (referred to as E oil), and four samples were prepared by the steam distillation method (referred to as SD oil). Five E oils enhanced singlet oxygen production. As these essential oils may be phototoxic, it should be used for their use whit light. Two E oils and three SD oils showed singlet oxygen scavenging activity. These results may suggest that the antioxidant activity of essential oils are judged from their radical scavenging activity. Essential oils, which enhance the singlet oxygen production and show higher cytotoxicity, may contain much of limonene. These results suggest that limonene is involved not only in the enhancement of singlet oxygen production but also in the expression of cytotoxic activity, and that attention has to be necessary for use of blended essential oils.

A fullerene core to probe dendritic shielding effects

Dendrimers with a C 60 core have been obtained by cyclization of dendritic bis-malonate derivatives at the carbon sphere. The resulting bis-methanofullerene derivatives have been characterised by electrospray (ES) and/or MALDI-TOF mass spectrometries. UV–VIS absorption spectra, fluorescence spectra, and fullerene singlet excited state lifetimes have been determined in solvents of different polarity (toluene, dichloromethane, acetonitrile). These data suggest a tighter core/periphery contact upon increase of solvent polarity and dendrimer size. In all the investigated solvents, the fullerene triplet lifetimes are steadily increased with the dendrimer volume, reflecting lower diffusion rates of O 2 inside the dendrimers along the series. Measurements of quantum yields of singlet oxygen sensitization indicate that longer lived triplet states generate lower amounts of singlet oxygen ( 1O 2 ∗) in dichloromethane but not in apolar toluene suggesting a tighter contact between the dendritic branches and the fullerene core in CH 2Cl 2. In acetonitrile, the trend in singlet oxygen production is peculiar. Effectively, enhanced singlet oxygen production is monitored for the largest dendrimer. This reflects specific interactions of excited 1O 2 ∗ molecules with the dendritic wedges, as probed by singlet oxygen lifetime measurements, possibly as a consequence of trapping effects.

Synthesis and photobiological properties of acetylpsoralen derivatives

In an investigation to find monofunctional reactants for DNA which can act as new agents in the photochemotherapy of psoriasis, we have synthesized and studied some methylpsoralen derivatives which contain an acetyl group at one of the two reactive sites of the furocoumarin skeleton (at the 3 or 5′ positions). The compounds do not react easily with DNA; their photobiological properties ( e.g. the lack of an ability to inhibit DNA synthesis in Ehrlich ascites tumour cells, to induce T2 phage sensitization and to induce erythema in guinea-pig skin) are exactly in line with this behaviour. Some interesting features are shown by 4,8-dimethyl-5′-acetylpsoralen: it is capable of producing a very large amount of singlet oxygen — an order of magnitude higher than the other compounds and 8-methoxypsoralen (used as reference). In spite of this property, 4,8-dimethyl-5′- acetylpsoralen is non-phototoxic to the skin, and its other photobiological properties appear to be in line with its lack of interaction with DNA rather than its enhanced singlet oxygen production.