Efficiency Of Singlet Oxygen Production Research Articles

Non-peripherally alkylamino-substituted phthalocyanines: Synthesis, spectral, photophysical and acid-base properties

Non-peripherally substituted metal-free and zinc phthalocyanines (Pcs) bearing four diethylamino groups and four Br atoms were prepared. Optimal conditions for synthesis of corresponding precursor ([Formula: see text] 3-bromo-6-(diethylamino)phthalonitrile) either by nucleophilic substitution or by Buchwald–Hartwig coupling were studied. Noteworthy, 3,6-bis(diethylamino)phthalonitrile was also formed, nevertheless only at low yield (typically below 1%) and all attempts for its cyclotetramerization failed. Q bands of prepared Pcs were strongly red shifted up to the near-IR region (769 and 800 nm in THF for zinc and metal-free Pc, respectively). Unusually large hypsochromic shifts of the Q bands, 130 and 80 nm for metal-free and zinc Pc, respectively, were observed upon treating these Pcs with trifluoroacetic acid, which was attributed to the protonation of non-peripheral amines. Treatment with sulfuric acid led to subsequent protonation on the azomethine nitrogens as well. Photophysical study revealed low fluorescence emission of both derivatives ([Formula: see text] <0.03, in THF) and efficient singlet oxygen production only for zinc Pc ([Formula: see text] 0.77 in THF and 0.60 in DMF).

Click synthesis of glycosylated porphyrin-cored PAMAM dendrimers with specific recognition and thermosensitivity

Glycoporphyrin dendrimers have received increasing attentions due to their distinct physical and chemistry properties, such as fluorescence and water solubility. They also acted as a promising photodynamic therapy (PDT) sensitizer and used in the study of carbohydrate-protein interaction. In this study, different generations of porphyrin-cored dendrimers consisting of glycosylated siloxane-poly (amido amine) typed dendron (PP-Si-PAMAM-Dm-Lac, m = 1, 2, and 3), multifunctional specific-targeting sensitizers, had been synthesized via click reaction. The structure of PP-Si-PAMAM-Dm-Lac was characterized by 1H NMR, GPC, FT-IR, UV-vis and fluorescence analyses. This glycoporphyrin dendrimers, not only obtained high fluorescence quantum yield and singlet oxygen production efficiency, but also showed specific recognition of lectin and remarkable temperature-responsive property (20–80 °C). These properties proved a facile click synthetic strategy of glycosylated siloxane-poly (amido amine) typed dendrimers with multiple functions as a promising tumor-selective photsensitizer (PS) for PDT and also allow applications in highly sensitive fluorescent probes over a larger temperature window.

Red/Near‐Infrared Emissive Metalloporphyrin‐Based Nanodots for Magnetic Resonance Imaging‐Guided Photodynamic Therapy In Vivo

AbstractNear‐infrared emissive (NIR) porphyrin‐implanted carbon nanodots (PCNDs or MPCNDs) are prepared by selectively carbonization of free base or metal complexes [M = Zn(II) or Mn(III)] of tetra‐(meso‐aminophenyl)porphyrin in the presence of citric acid. The as‐prepared nanodots exhibit spontaneously NIR emission, small size, good aqueous dispersibility, and favorable biocompatibility characteristic of both porphyrins and pristine carbon nanodots. The subcellular localization experiment of nanodots indicates a lysosome‐targeting feature. And the in vitro photodynamic therapy (PDT) results on HeLa cells indicate the nanodots alone have no adverse effect on tumor cells, but display remarkable photodynamic efficacy upon irradiation. Moreover, MnPCNDs containing paramagnetic Mn(III) ions, which possesses good biocompatibility, NIR luminescence, and magnetic resonance imaging and efficient singlet oxygen production, are further studied in magnetic resonance imaging‐guided photodynamic therapy in vivo.

Highly efficient organic photosensitizer with aggregation-induced emission for imaging-guided photodynamic ablation of cancer cells

We design an organic photosensitizer with a donor-π-acceptor configuration. The photosensitizer exhibits aggregation-induced emission characteristics and efficient singlet oxygen production in the aggregated state. It is then enveloped into the water-soluble micelle to afford a nanoprobe. The water-soluble nanoprobe keeps the photosensitizer in the aggregation state and is used for imaging-guided photodynamic ablation of cancer cells.

Saline hybrid nanoparticles with phthalocyanine and tetraphenylporphine anions showing efficient singlet-oxygen production and photocatalysis.

The inorganic-organic hybrid nanoparticles Gd43+[AlPCS4]34- and La43+[TPPS4]34- ([AlPCS4]4-: aluminium(iii) chlorido phthalocyanine tetrasulfonate; [TPPS4]4-: tetraphenylporphine sulfonate) are shown for the first time. Both were obtained via aqueous synthesis and contain extremely high contents of [AlPCS4]34- (81 wt%) and [TPPS4]34- (83 wt%). They show efficient singlet oxygen (1O2) production upon daylight and red-light irradiation. Photocatalysis is evidenced via dye degradation as a proof-of-the-concept and proceeds with daylight and even red-light illumination.

Folic Acid–Conjugated Pyropheophorbide a as the Photosensitizer Tested for In Vivo Targeted Photodynamic Therapy

Photodynamic therapy (PDT) is a highly localized and minimally invasive cancer treatment modality with many important advantages, but the lack of ideal photosensitizers (PSs) greatly restricts its clinical utility. To develop new PSs with highly efficient singlet oxygen production and high tumor-localizing ability to reduce damage to healthy adjacent tissues, we conjugated folic acid (FA) with pyropheophorbide a (Pyro), a potent PS with a very high singlet oxygen quantum yield and a high extinction coefficient. In the present work, we describe the synthesis and PDT evaluation of this FA–Pyro conjugate both in vitro and in vivo. This conjugation increased the accumulation of Pyro inside the tumors and improved the efficiency of PDT, resulting in eradication of subcutaneous xenograft KB (human mouth epidermal carcinoma) tumors after only 1 or 2 applications of external near infrared light irradiation. This outstanding PDT outcome in a tumor-bearing mouse model and the simple synthesis of the conjugate should have very good practical potential for clinical application.

A comparative study of the processes of generation of singlet oxygen upon irradiation of aqueous preparations on the basis of chlorin e6 and coproporphyrin III

The photosensitizing ability of an agent based on chlorin e6 (Photoditazin), which is used for photodynamic diagnosis and therapy, is compared with that of a new preparation on the basis of coproporphyrin III in the environment of a phosphate buffer and a simulated biological environment (albumin solution). The efficiency of singlet-oxygen production was estimated by EPR spectroscopy and spectroscopy in the UV and visible ranges with the use of “chemical traps” of singlet oxygen. By irradiating drugs with LED emission centered at λmax = 520 nm, we determined the quantum yield of singlet-oxygen production in a buffer solution; the obtained values are 0.60 and 0.37 for chlorine and coproporphyrin, respectively. The steady-state concentration of singlet oxygen upon irradiation of solutions of the studied photosensitizers with concentrations of 12–43 μМ and the density of radiation power within the 6–96 W/cm2 region was found to be in the region of 1010–1011 molecules/cm3. It is shown that the introduction into the solution of egg albumin (0.1%) reduces the sensitizing properties of the two drugs by two to three times, while the efficiencies of the preparations with respect to singlet-oxygen production become almost identical (0.19 and 0.17).

Iron oxide nanoparticles functionalized with novel hydrophobic and hydrophilic porphyrins as potential agents for photodynamic therapy

The preparation of novel porphyrin derivatives and their immobilization onto iron oxide nanoparticles to build up suitable nanotools for potential use in photodynamic therapy (PDT) has been explored. To achieve this purpose, a zinc porphyrin derivative, ZnPR-COOH, has been synthesized, characterized at the molecular level and immobilized onto previously synthesized iron oxide nanoparticles covered with oleylamine. The novel nanosystem (ZnPR-IONP) has been thoroughly characterized by a variety of techniques such as UV–Vis absorption spectroscopy, fluorescence spectroscopy, X-ray photoloectron spectroscopy (XPS) and transmission electron microscopy (TEM). In order to probe the capability of the photosensitizer for PDT, the singlet oxygen production of both ZnPR-IONP and the free ligand ZnPR-COOH have been quantified by measuring the decay in absorption of the anthracene derivative 9,10-anthracenedipropionic acid (ADPA), showing an important increase on singlet oxygen production when the porphyrin is incorporated onto the IONP (ZnPR-IONP).On the other hand, the porphyrin derivative PR-TRIS3OH, incorporating several polar groups (TRIS), was synthesized and immobilized with the intention of obtaining water soluble nanosystems (PR-TRIS-IONP). When the singlet oxygen production ability was evaluated, the values obtained were similar to ZnPR-COOH/ZnPR-IONP, again much higher in the case of the nanoparticles PR-TRIS-IONP, with more than a twofold increase. The efficient singlet oxygen production of PR-TRIS-IONP together with their water solubility, points to the great promise that these new nanotools represent for PDT.

Nanosized ZSM-5 will improve photodynamic therapy using Methylene blue

Nowadays, nanotechnology is growing to improve Photodynamic Therapy and reduce its side effects. In this research, the synthesized co-polymeric Zeolite Secony Mobile-5 (ZSM-5) was employed to modify Methylene Blue (MB) for these reasons. UV–Visible, FTIR, XRD analysis and SEM images were used to investigate obtained nanostructure. The crystal size for these nanostructures were determined 75nm and maximum adsorption capacity of MB in the nanostructure was estimated 111 (mgg−1). Also, the role of Polyethylene Glycol (PEG) was studied as a capable non-toxic polymeric coating to overcome biological barriers. Moreover, potential of singlet oxygen production of the synthesized nanostructure was compared with MB and ZSM-5 nanoparticles control samples. Synthesized nanodrugs show impressive light induced singlet oxygen production efficiency.

Modelling energy deposition in nanoscintillators to predict the efficiency of the X-ray-induced photodynamic effect.

Scintillating nanoparticles (NPs) in combination with X-ray or γ-radiation have a great potential for deep-tissue cancer therapy because they can be used to locally activate photosensitizers and generate singlet oxygen in tumours by means of the photodynamic effect. To understand the complex spatial distribution of energy deposition in a macroscopic volume of water loaded with nanoscintillators, we have developed a GEANT4-based Monte Carlo program. We thus obtain estimates of the maximum expected efficiency of singlet oxygen production for various materials coupled to PS, X-ray energies, NP concentrations and NP sizes. A new parameter, ηnano, is introduced to quantify the fraction of energy that is deposited in the NPs themselves, which is crucial for the efficiency of singlet oxygen production but has not been taken into account adequately so far. We furthermore emphasise the substantial contribution of primary interactions taking place in water, particularly under irradiation with high energy photons. The interplay of all these contributions to the photodynamic effect has to be taken into account in order to optimize nanoscintillators for therapeutic applications.

Binding Studies of Small Molecules to Telomeric Quadruplex DNA for Targeted Singlet Oxygen Production

Recent studies [Shieh et al., ACSNano (2010), 4, 1433; Yin et al., Chem. Comm (2012), 48, 6556] have suggested that G-quadruplexed DNA (qDNA) structures can serve as carriers for targeted delivery of photosensitizers in photodynamic therapies. In our studies, we have investigated the in vitro singlet oxygen production from the photosensitive porphyrins, N-methyl mesoporphyrin IX (NMM) and 5,10,15,20-tetrakis(N-methyl-4-pyridyl)-21H,23H-porphine tetratosylate (TMPyP4), when bound to both calf thymus duplex DNA (ct-DNA) and K+-stabilized G-quadruplexed human (hTTAGGG)4 telomeric DNA (qDNA). Competition micro-dialysis assays confirmed selective binding of NMM to the mixed hybrid qDNA conformation over TMPyP4, which binds non-selectively to both qDNA and ct-DNA. Sensitized singlet oxygen production was detected using the fluorescent singlet oxygen sensor green (SOSG) assay immediately following porphyrin-DNA irradiation. First-order singlet oxygen generation was detected for both NMM and TMPyP4 when bound to qDNA. However, no appreciable singlet oxygen production was detected for NMM when bound to ct-DNA suggesting potential targeted chemotherapeutic applications for NMM bound to qDNA. CD-studies suggest no change in conformation of the qDNA following irradiation. Currently, we are investigating the effect of the Na+-stabilized antiparallel qDNA conformation on rate and efficiency of singlet oxygen production from these porphyrins. (Supported by NIH-SCORE GM 095437-04.)

Synthesis and investigation of singlet oxygen production efficiency of photosensitizers based on meso-phenyl-2,5-thienylene linked porphyrin oligomers and polymers

Three new Zn(ii)-, oligo- and poly(2,5-thienylene)-linked porphyrins, bearing multiple triethylene glycol (TEG) groups, on all meso aryl positions were synthesized via Stille and Suzuki coupling reactions and their photophysical properties as well as singlet oxygen generation efficiencies have been investigated to elucidate the possibility of their use as a photosensitizer for photodynamic therapy (PDT) and photodynamic inactivation of bacteria.

π-π Stacking induced enhanced molecular solubilization, singlet oxygen production, and retention of a photosensitizer loaded in thermosensitive polymeric micelles.

Cancer photodynamic therapy (PDT) by photosensitizers (PS)-loaded polymeric micelles (PM) is hampered by the tendency of PS to aggregate in PM and/or by premature release of PS in the blood circulation. In the present study, aromatic thermosensitive PM, characterized by π-π stacking interaction, are used to encapsulate an axially solketal-substituted silicon phthalocyanine (Si(sol)2 Pc) with enhanced loading capacity, smaller size, and significantly improved retention of Si(sol)2 Pc compared with systems based on thermosensitive PM lacking aromatic groups. Interestingly, Si(sol)2 Pc is much less prone to aggregation in the aromatic PM, i.e., the amount of Si(sol)2 Pc that could be encapsulated without aggregation is 330 times higher in the aromatic PM than in the nonaromatic PM. Furthermore, Si(sol)2 Pc in the aromatic PM in a molecularly dissolved (non-aggregated) form displays three times more efficient singlet oxygen production than Si(sol)2 Pc aggregated in the non-aromatic PM. As a result, the photocytotoxicity of Si(sol)2 Pc-loaded aromatic PM to B16F10 cells is increased, compared with that of the non-aromatic PM, while no significant cytotoxicity is observed in the dark. Fluorescence-activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM) analysis shows cell uptake of Si(sol)2 Pc loaded in the aromatic PM, and the Si(sol)2 Pc is taken up by the cells together with the micelles. The efficient singlet oxygen production of Si(sol)2 Pc dissolved in the aromatic PM makes it an interesting formulation for cancer PDT.

Sinoporphyrin sodium, a novel sensitizer, triggers mitochondrial-dependent apoptosis in ECA-109 cells via production of reactive oxygen species.

BackgroundSonodynamic therapy (SDT) is a promising method that uses ultrasound to activate certain chemical sensitizers for the treatment of cancer. The purpose of this study was to investigate the sonoactivity of a novel sensitizer, sinoporphyrin sodium (DVDMS), and its sonotoxicity in an esophageal cancer (ECA-109) cell line.MethodsThe fluorescence intensity of DVDMS, hematoporphyrin, protoporphyrin IX, and Photofrin II was detected by fluorescence microscopy and flow cytometry. Generation of singlet oxygen was measured using a 1, 3-diphenylisobenzofuran experiment. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay was used to examine cell viability. Production of reactive oxygen species (ROS) and destabilization of the mitochondrial membrane potential were assessed by flow cytometry. Apoptosis was analyzed using Annexin-PE/7-amino-actinomycin D staining. Confocal microscopy was performed to assess mitochondrial damage and identify release of cytochrome C after treatment. Western blots were used to determine expression of oxidative stress-related and apoptosis-associated protein. Ultrastructural changes in the cell were studied by scanning electron microscopy.ResultsDVDMS showed higher autofluorescence intensity and singlet oxygen production efficiency compared with other photosensitizers in both cancerous and normal cells. Compared with hematoporphyrin, DVDMS-mediated SDT was more cytotoxic in ECA-109 cells. Abundant intracellular ROS was found in the SDT groups, and the cytotoxicity induced by SDT was effectively remitted by ROS scavengers. DVDMS located mainly to the mitochondria of ECA-109 cells, which were seriously damaged after exposure to SDT. Release of cytochrome C, an increased rate of apoptosis, and activated apoptosis protein were detected in the SDT group. In addition, relatively severe cell damage was observed on scanning electron microscopy after treatment with DVDMS and SDT.ConclusionThese results suggest that DVDMS could be activated by ultrasound, and that DVDMS mediates SDT-induced mitochondrial-dependent apoptosis in ECA-109 cells via production of ROS.

Revisiting the photophysics and photochemistry of methylene violet (MV)

Methylene violet (MV) is known for its photosensitizing properties for singlet oxygen (1O2) generation upon visible-light irradiation and various examples of its potential use in photodynamic inactivation of microorganisms and for photomedicinal purposes were reported. Notwithstanding its good photosensitization properties, there is a loss of clinical tests in the recent literature, probably related to the incomplete information concerning the photophysics of this dye and the effects of the medium on its properties. We thus studied both experimentally and numerically the solvatochromic effects and the presence of acids on the absorption and fluorescence spectra of MV. In chloroform, the highly favoured and reversible formation of a mono-protonated derivative of MV, MVH+, was clearly demonstrated experimentally and supported by ab-initio calculations. In acetonitrile, the more complex experimental absorption bands can be explained by several assumptions including a thermodynamic equilibrium between MVH+ and MVH22+ or the formation of a possibly oblique dimer (MVH+)2 induced by the formation of intermolecular hydrogen bonds. All these data point out to the high sensitivity of MV to intermolecular hydrogen bonding and to protonation, inducing a significant influence of the chemical environment on the photosensitization mechanisms of MV: from transient spectroscopy and photochemical experiments, an electron transfer side-mechanisms was shown to occur only in aprotic solvents, together with a very general and efficient singlet oxygen production whatever the solvent. MV thus represents a very good singlet oxygen sensitizer even though the influence of the chemical environment should be carefully considered for any application. Moreover, MV might be a sensitive probe for the detection of acids in organic non-protic solvents.

A Supermolecular Photosensitizer with Excellent Anticancer Performance in Photodynamic Therapy

A supermolecular photosensitizer with excellent anticancer behavior when used for photodynamic therapy (PDT) is fabricated by the incorporation of zinc phthalocyanines (ZnPc) into the gallery of a layered double hydroxide (LDH). The composite material possesses uniform particle size (hydrodynamic diameter ∼120 nm), and the host–guest and guest–guest interactions result in a high dispersion of ZnPc in a monomeric state in the interlayer region of the LDH matrix, with high singlet oxygen production efficiency. In vitro tests performed with HepG2 cells reveal a satisfactory PDT effectiveness of the ZnPc(1.5%)/LDH composite photosensitizer: a cellular damage as high as 85.7% is achieved with a rather low dosage of ZnPc (10 μg/mL). An extraordinarily high specific efficacy is demonstrated (31.59 μg−1 (J/cm2)−1), which is over 185.5% enhancement compared with the previously reported photosensitizers under similar test conditions. Furthermore, an in vivo study of the ZnPc(1.5%)/LDH demonstrates excellent PDT performance with an ultra‐low dose (0.3 mg/kg) and a low optical fluence rate (54 J/cm2). In addition, the ZnPc/LDH photosensitizer displays high stability, good biocompatibility, and low cytotoxicity, which would guarantee its practical application. Therefore, this work provides a facile approach for design and fabrication of inorganic–organic supermolecular materials with greatly enhanced anticancer behavior.

Immobilized Organic Photosensitizers with Versatile Reactivity for Various Visible‐Light Applications

Various photosensitizers were grafted by conventional peptide coupling methods to functionalized silica with several macroscopic shapes (powders, films) or embedded in highly transparent and microporous silica xerogel monoliths. Owing to the transparency and free-standing shape of the monoliths, the transient species arising from irradiation of the PSs could be analyzed and were not strikingly different from those observed in solutions. The observed reactivity for either liquid-solid (α-terpinene oxygenation vs dehydrogenation) or gas-solid (dimethylsulfide, DMS, solvent-free oxidation) reactions was consistent with the properties of the excited states of the PSs under consideration. Immobilized anthraquinone-derived materials preferentially react in both cases by electron transfer from the substrate to the triplet state of the sensitizer, in spite of an efficient singlet oxygen production. The recently developed 9,14-dicyanobenzo[b]triphenylene-3-carboxylic acid, DBTP-COOH, efficiently reacts via energy transfer to yield singlet oxygen from its triplet state. It was shown to perform better than 9,10-dicyanoanthracene and rose bengal for DMS oxidation and α-terpinene photooxygenation to ascaridole, respectively. Thus, by a proper choice of the organic immobilized photocatalyst, it is possible to develop efficient and reusable materials, activated under visible light, for various applications and to tune the reaction pathway, opening the way to green oxidation processes.

Synthesis of novel octa-cationic and non-ionic 1,2-ethanediamine substituted zinc (Ⅱ) phthalocyanines and their in vitro anti-cancer activity comparison

Novel tetra-substituted zinc phthalocyanines (Pcs) bearing 1,2-ethanediamine group and the quaternized derivatives were synthesized and characterized. The photophysical and cellular properties of these Pcs were investigated. The results indicated that the quaternized ionic effect can greatly improve the water-solubility of Pcs and reduce their aggregation degree in aqueous solution. Comparative studies with quaternized phthalocyanine and its unquaternized counterpart have also demonstrated that the quaternary action on the molecules significantly enhances the fluorescence quantum yields, fluorescence lifetimes, efficiency of singlet oxygen production and, thereby, the in vitro photodynamic therapy efficacy.

Sweet chiral porphyrins as singlet oxygen sensitizers for asymmetric Type II photooxygenation

Carbohydrate-decorated meso-tetraarylporphyrins P-G and P-C were synthesized via Lewis-acid catalyzed condensation of acetylated carbohydrate-substituted benzaldehydes and pyrrole. Their efficiency of singlet oxygen production was compared with the corresponding non-substituted porphyrin. The oxidation of the spin trap molecule TEMP (2,2,6,6-tetramethyl-4-piperidone) by singlet oxygen to TEMPO was measured by ESR spectroscopy, showing higher reaction rates for the sugar porphyrins. These results were corroborate by laser flash photolysis measurements that resulted in higher triplet lifetimes of glucosyl- and cellobiosyl porphyrins in comparison with tetrakis(4-hydroxyphenyl)porphyrin. Low ee was detected in the photooxygenation of ethyl tiglate.

Photosensitizer-doped conjugated polymer nanoparticles with high cross-sections for one- and two-photon excitation

We report a novel nanoparticle that is promising for photodynamic therapy applications, which consists of a π-conjugated polymer doped with a singlet oxygen photosensitizer. The nanoparticles exhibit highly efficient collection of excitation light due to the large excitation cross-section of the polymer. A quantum efficiency of singlet oxygen production of 0.5 was determined. Extraordinarily large two-photon excitation cross-sections were determined, indicating promise for near infrared multiphoton photodynamic therapy. Gel electrophoresis of DNA after near-UV irradiation in the presence of nanoparticles indicated both purine base and backbone DNA damage.