High Singlet Oxygen Quantum Yield Research Articles

Antitumor effects evaluation of a novel porphyrin derivative in photodynamic therapy.

In this paper, the antitumor activity of a novel porphyrin-based photosensitizer 5,10,15,20-tetrakis[(5-diethylamino)pentyl] porphyrin (TDPP) was reported in vitro and in vivo. The photophysical and cellular properties of TDPP were investigated. The singlet oxygen generation quantum yield of TDPP was detected; it showed a high singlet oxygen quantum yield of 0.52. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The efficiency of TDPP-photodynamic therapy (PDT) in vitro was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and in situ trypan blue exclusion test. Treated with a 630-nm laser, TDPP can kill cultured human esophageal cancer cell line (Eca-109) cells and reduce the growth of Eca-109 xenograft tumors significantly in BABL/c nude mice. And histopathological study was also used to confirm the antitumor effect. It has the perspective to be developed as a new antitumor drug in photodynamic therapy and deserves further investigation.

Porpholactone and Metal Complexes: Effect of Lactonization of ß-Pyrrole

The development of “porphyrin-like” molecules (porphyrinoids) and related tetrapyrroles has attracted considerable attention for the potential as optical materials and photosensitizers for photodynamic therapy (PDT). Porpholactones (TPPLs) are an important but relatively unstudied class of tetrapyrroles, which combine some of the features of porphyrins and chlorins. To explore the effect ß-Lactonization on the electronic structures and spectral properties is of importance to expand the porpholactone chemistry. In recent years, we focused on the synthesis, characterization and the application of porpholactone and their metal complexes. Based on the skeleton of porpholactones, the β-lactone moiety provides an access to tune their NIR optical characteristics, amphilicity and cellular behaviour. More importantly, the relative orientation of the β-dilactone moieties significantly influences their electronic structures and photophysical properties, for example, the Qy band of trans-porphodilactone is red shifted 19 nm compared to that of the cis-isomer with a 2-fold increase in the absorption intensity. Trans-isomer exhibit much higher singlet oxygen quantum yield and the related PDT efficiency than cis-isomer upon irradiation at their Qv bands, respectively. Thus, these results reveal the importance of relative orientation of b-substituents on optical properties at NIR regions.

Fabrication of thermosensitive, star-shaped poly(L-lactide)-block-poly(N-isopropylacrylamide) copolymers with porphyrin core for photodynamic therapy

Thermosensitive, star-shaped porphyrin-cored poly(L-lactide)-block-poly(N-isopropylacrylamide) (SPPLA–PNIPAM) was synthesized via ring-opening polymerization (ROP) and reversible addition–fragmentation chain transfer polymerization (RAFT). The composition and properties of copolymer were discussed based on the results of NMR, IR and GPC. With PNIPAM block length decreasing, the morphology of SPPLA–PNIPAM copolymer in aqueous solution transformed hierarchically from spherical micelles through wormlike micelles to vesicles, and the lower critical solution temperatures (LCST) of the copolymer solutions were determined to be 37.9°, 37.2°, 35.9°, respectively. The in vitro study indicated that SPPLA–PNIPAM showed no significant dark cytotoxicity at concentrations up to 128μg/mL, while showed apparent phototoxicity toward BEL-7402 cancer cells. Considering a high singlet oxygen quantum yield and suitable nominal physiologic LCST, it is expected that the SPPLA–PNIPAM copolymer is a promising stimulus-responsive candidate which has a potential application in photodynamic therapy (PDT).

Singlet oxygen photosensitisation by the fluorescent protein Pp2FbFP L30M, a novel derivative of Pseudomonas putida flavin-binding Pp2FbFP.

Flavin-binding fluorescent proteins (FbFPs) are a class of fluorescent reporters that have been increasingly used as reporters in the study of cellular structures and dynamics. Flavin's intrinsic high singlet oxygen ((1)O2) quantum yield (ΦΔ = 0.51) provides a basis for the development of new FbFP mutants capable of photosensitising (1)O2 for mechanistic and therapeutic applications, as recently exemplified by the FbFP miniSOG. In the present work we report an investigation on the (1)O2 photoproduction by Pp2FbFP L30M, a novel derivative of Pseudomonas putida Pp2FbFP. Direct detection of (1)O2 through its phosphorescence at 1275 nm yielded the value ΦΔ = 0.09 ± 0.01, which is the highest (1)O2 quantum yield reported to date for any FP and is approximately 3-fold higher than the ΦΔ for miniSOG. Unlike miniSOG, transient absorption measurements revealed the existence of two independent triplet states each with a different ability to sensitise (1)O2.

Spectral Properties of Water-Soluble Conjugated Polymer PFP/DNA/Porphyrin Complex

Photodynamic therapy (PDT) is a particular treatment of tumors, which localizes the biological responses by the way that light is applied. In this paper, we have designed a water-soluble system potentially for PDT, which could selectively generate singlet oxygen efficiently under both of one-and two-photon excitation. This complex consists of a cationic water-soluble conjugated polymer PFP, anionic DNA and a cationic porphyrin. The cationic conjugated polymer PFP and porphyrin are connected by anionic DNA through electrostatic interactions. Energy transfer from conjugated polymer PFP (donor) to porphyrin (acceptor) is available since the considerable overlapping between the emission of donor and the absorption of acceptor (S-0 -> S-2). Steady-state spectra and fluorescence lifetime measurements have been performed on the complex with different DNA sequences in order to achieve the energy transfer efficiency. The results of steady-state fluorescence spectra show that there is a remarkable change of fluorescence intensity of the complex with G-quadruplex DNA, which indicates significant energy transfer from the donor to the acceptor. Furthermore, the greatest change of fluorescence lifetime measured by means of time-correlated single photon counting (TCSPC) also proves the highest energy transfer efficiency of the system with G-quadruplex DNA. Singlet oxygen quantum yield can be obtained by the detection of singlet oxygen emission spectra. Porphyrin bound to G-quadruplex DNA has the highest singlet oxygen quantum yield, which suggests this system a possible application in PDT since singlet oxygen could kill tumor cells. Two-photon absorption cross section has also been measured, which reflects the light-harvesting efficiency of the conjugated polymer PFP. The result shows that the conjugated polymer PFP owns large two-photon absorption cross section in the region of 720 similar to 850 nm where the transmission in tissue is higher compared to the visible light. The energy transfer efficiency and singlet oxygen quantum yield are both selective for different DNA sequences. G-quadruplex DNA that is very rich in tumor cells has the highest selectivity, which makes this system a potential application in PDT.

Physicochemical and photodynamic antimicrobial chemotherapy studies of mono- and tetra-pyridyloxy substituted indium(III) phthalocyanines

Abstract The synthesis and photophysicochemical properties of mono- and tetra-pyridyloxy substituted indium(III) phthalocyanines (InPcs) are presented in this study. General trends are described for quantum yields of fluorescence, triplet, singlet oxygen and photodegradation as well as lifetimes of fluorescence and triplet state of these compounds. The complexes exhibited high singlet oxygen quantum yields ( Ф Δ ) ranging from 0.44 to 0.66 in DMF, and from 0.44 to 0.69 in DMSO and Ф Δ = 0.31 for the quartenized tetra substituted InPc which is soluble in water. The triplet quantum yields ( Ф T ) ranged from 0.77 to 0.95 in DMF and from 0.77 to 0.94) in DMSO. The tetra substituted photosensitizers do not differ in their inactivation of bacteria with over 8 log reduction of viable bacteria when compared with the mono substituted photosensitizer which could only manage a 1 log reduction.

The effect of amphiphilic polymers on the association, morphology and photophysical properties of hypocrellin coordination polymer/fullerene assemblies.

The yttrium coordination polymer of pyrene modified hypocrellin A (Y(3+)-PyrHA) is synthesized and characterized. The methoxydiglycol malonate modified fullerene can be included in the cavity of Y(3+)-PyrHA in organic solution and buffer solution containing amphiphilic polymers, such as polyvinyl pyrrolidone (PVP), pluronic F127 and P123. The interaction between an amphiphilic polymer and Y(3+)-PyrHA plays an important role in controlling the size and morphology of Y(3+)-PyrHA/fullerene. TEM images of Y(3+)-PyrHA/fullerene in 1% F127 and P123 show nanoparticles in the size range 10-60 nm, while TEM images of Y(3+)-PyrHA/fullerene in 1% PVP display large-scale aggregation. Singlet oxygen is generated by irradiation of the polymer solution of Y(3+)-PyrHA/fullerene in the presence of oxygen. The electron paramagnetic resonance (EPR) spin trapping and 9,10-dimethoxyanthracene-2-sulfonic acid sodium salt (MAS) photooxidation results suggest that in 1% P123 solution Y(3+)-PyrHA/fullerene exhibits a higher singlet oxygen quantum yield than Y(3+)-PyrHA and the corresponding fullerene.

Oligolysine‐Conjugated Zinc(II) Phthalocyanines as Efficient Photosensitizers for Antimicrobial Photodynamic Therapy

A series of zinc(II) phthalocyanines conjugated with an oligolysine chain (n=2, 4, and 8) were synthesized and characterized by using various spectroscopic methods. As shown by using UV/Vis and fluorescence spectroscopic methods, these compounds were nonaggregated in N,N-dimethylformamide, and gave a weak fluorescence emission and high singlet oxygen quantum yield (Φ(Δ) =0.86-0.89) as a result of their di-α-substitution. They became slightly aggregated in water with 0.05 % Cremophor EL, but they could still generate singlet oxygen effectively. The antimicrobial photodynamic activities of these compounds were then examined against various bacterial strains, including the Gram-positive methicillin-sensitive Staphylococcus aureus ATCC 25923 and methicillin-resistant Staphylococcus aureus ATCC BAA-43, and the Gram-negative Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 27853. Generally, the dyes were much more potent toward the Gram-positive bacteria. Only 15 to 90 nM of these photosensitizers was required to induce a 4 log reduction in the cell viability of the strains. For Escherichia coli, the photocytotoxicity increased with the length of the oligolysine chain. The octalysine derivative showed the highest potency with a 4 log reduction concentration of 0.8 μM. Pseudomonas aeruginosa was most resistant to the photodynamic treatment. The potency of the tetralysine derivative toward a series of clinical strains of Staphylococcus aureus was also examined and found to be comparable with that toward the nonclinical counterparts. Moreover, the efficacy of these compounds in photodynamic inactivation of viruses was also examined. They were highly photocytotoxic against the enveloped viruses influenza A virus (H1N1) and herpes simplex virus type 1 (HSV1), but exhibited no significant cytotoxicity against the nonenveloped viruses adenovirus type 3 (Ad3) or coxsackievirus (Cox B1). The octalysine derivative also showed the highest potency with an IC(50) value of 0.05 nM for the two enveloped viruses.

Synthesis, photophysicochemical properties and TD-DFT calculations of tetrakis(2-benzoyl-4-chlorophenoxy) phthalocyanines

The synthesis of metal free, magnesium and zinc tetrakis(2-benzoyl-4-chlorophenoxy) phthalocyanine derivatives (2–4) is described along with their characterization by elemental analysis, IR, UV-visible absorption, and 1 H NMR spectroscopy and mass spectrometry. Trends observed in the fluorescence, triplet state, singlet oxygen and photodegradation quantum yields and the triplet state lifetimes are also analyzed. The compounds exhibit high solubility in a wide range of organic solvents and no evidence of aggregation was observed over a wide concentration range. The Zn ( II ) complex (4) was found to have a very high singlet oxygen quantum yield (ΦΔ = 0.78) in dimethylsulfoxide (DMSO) and a reasonably large triplet state quantum yield (ΦT = 0.82). The photophysical and photochemical properties clearly demonstrate that these compounds could prove useful in singlet oxygen applications such as photodynamic therapy (PDT). DFT and TD-DFT calculations were used to assess the impact of the positional isomerism of the 2-benzoyl-4-chlorophenoxy substituents on the electronic structures and optical spectroscopy.

Optical nonlinearities and photophysicochemical behaviour of green and blue forms of lutetium bisphthalocyanines

A rare earth sandwich-type phthalocyanine: bis-{2,3,9,10,16,17,23,24-octa(4-tert-butylphenoxy) phthalocyaninato} lutetium(III) has been synthesized. The photophysical and nonlinear optical behavior of both the “green” and “blue” forms ([LuIIIPc2] and [LuIIIPc2]−, respectively) of the complex have been investigated. High triplet state and singlet oxygen quantum yield values were obtained for the neutral blue form which contains no unpaired electrons. Relatively high third order susceptibility and hyperpolarizability values of the order of 10−10 and 10−28 esu were obtained for both the green and blue forms, respectively. A very low threshold intensity of 0.00051 J cm−2 was obtained for the blue form. Hence the complex shows promise for non-linear optical applications.

Broadband Absorbing Polyporphyrin Membrane as Singlet Oxygen Photosensitizer for Photo‐oxidation

A novel polymer membrane (TPP‐M) with strong light harvesting ability within the entire visible‐ light spectrum has been prepared, in which the meso‐tetrakis(4‐cyanophenyl) porphyrin (TPP‐1) as a functional unit is highly crosslinked through an aromatic nitrile trimerization reaction. The designed triazine framework controls the size of the π‐conjugation and retains the excellent photophysical properties of monomeric porphyrin, such as strong absorption and high singlet oxygen quantum yield. Due to these excellent photophysical properties and low solubility in common organic solvents, polyporphyrin membranes, as efficient singlet oxygen (1O2) sensitizers, could be easily recycled and reused for the photo‐oxidation of 1,5‐dihydroxynaphthalene (DHN). image

Cell-Specific and pH-Activatable Rubyrin-Loaded Nanoparticles for Highly Selective Near-Infrared Photodynamic Therapy against Cancer

Spatiotemporal control of singlet oxygen ((1)O2) release is a major challenge for photodynamic therapy (PDT) against cancer with high therapeutic efficacy and minimum side effects. Here a selenium-rubyrin (NMe2Se4N2)-loaded nanoparticle functionalized with folate (FA) was designed and synthesized as an acidic pH-activatable targeted photosensitizer. The nanoparticles could specifically recognize cancer cells via the FA-FA receptor binding and were selectively taken up by cancer cells via receptor-mediated endocytosis to enter lysosomes, in which NMe2Se4N2 was activated to produce (1)O2. The pH-controllable release of (1)O2 specially damaged the lysosomes and thus killed cancer cells in a lysosome-associated pathway. The introduction of selenium into the rubyrin core enhanced the (1)O2 generation efficiency due to the heavy atom effect, and the substitution of dimethylaminophenyl moiety at meso-position led to the pH-controllable activation of NMe2Se4N2. Under near-infrared (NIR) irradiation, NMe2Se4N2 possessed high singlet oxygen quantum yield (ΦΔ) at an acidic pH (ΦΔ = 0.69 at pH 5.0 at 635 nm) and could be deactivated at physiological pH (ΦΔ = 0.06 at pH 7.4 at 635 nm). The subcellular location-confined pH-activatable photosensitization at NIR region and the cancer cell-targeting feature led to excellent capability to selectively kill cancer cells and prevent the damage to normal cells, which greatly lowered the side effects. Through intravenous injection of FA-NMe2Se4N2 nanoparticles in tumor-bearing mice, tumor elimination was observed after NIR irradiation. This work presents a new paradigm for specific PDT against cancer and provides a new avenue for preparation of highly efficient photosensitizers.

A Family of RuII Photosensitizers with High Singlet Oxygen Quantum Yield: Synthesis, Characterization, and Evaluation

AbstractA series of RuII‐based photosensitizers were synthesized and extensively characterized. The ligand utilized to coordinate ruthenium was a pyridine–quinoline hybrid bearing an anthracene moiety, and it was combined with commercially available 2,2′‐bipyridine (bpy) for the heteroleptic complexes. The produced bichromophoric complexes show very strong and wide UV/Vis absorption bands. The ability of these complexes to act as triplet photosensitizers in the production of singlet oxygen was thoroughly studied by utilizing the photooxidation of 1,3‐diphenylisobenzofuran as the test reaction. The most efficient photosensitizer in this new family of RuII complexes affords singlet oxygen quantum yields and production‐rate efficiencies up to two times higher than those of the benchmark [Ru(bpy)3]2+ parent complex.

The challenging combination of intense fluorescence and high singlet oxygen quantum yield in photostable chlorins — a contribution to theranostics

High fluorescence quantum yields, high singlet oxygen quantum yields and intense absorptions in the phototherapeutic window are fundamental properties for compounds intended for fluorescence diagnosis and photodynamic therapy. We report on photostable chlorins that combine these properties. The fluorinated tetraphenylchlorin FCMet has ΦF = 0.396 and ΦΔ = 0.58 ± 0.07, whereas F2CMet has ΦF = 0.360 and ΦΔ = 0.54 ± 0.05, and both have molar absorption coefficients larger than 30,000 M(-1) cm(-1) above 650 nm. These dual functional agents use nearly all the energy absorbed to perform the desired functions and are appropriate for theranostics applications.

Photophysical properties of erythrosin ester derivatives in ionic and non-ionic micelles

The xanthene dye erythrosin B (ERY) has high molar absorptivity and singlet oxygen quantum yield (ΦΔO21), which make it a potential photosensitizer for photodynamic applications. However, ERY is very hydrophilic in water at physiological pH due to its two negative charges, which results in low interaction with biological membranes. In this work we synthesized ester derivatives of ERY: methyl (ERYMET), butyl (ERYBUT) and decyl (ERYDEC) esters. The light absorption process was not greatly affected by the insertion of the alkyl group. The ester hydrophilic–lipophilic balance was evaluated by partition in a 1-octanol/water mixture. The insertion of the alkyl chain and the loss of one charge increased the hydrophobicity and, as expected, ERYDEC was the most hydrophobic dye. The interaction of the esters with the biological membranes was simulated in biomimetic models, micelles of: CTAB (cationic), SDS (anionic) and the polymeric surfactant pluronic F-127® and P-123® (non-charged). The order of the binding constants was ERY < ERYMET < ERYBUT < ERYDEC in all micelles investigated, equal to the hydrophobicity sequence. The localization of the dyes in micelles determined by quenching fluorescence measurements using iodide as a suppressor was consistent with their charge and hydrophobic characteristics. CTAB micelles showed a biphasic interaction due to the association of the cationic monomers of the surfactant and the anionic dyes. The fluorescence quantum yields of the esters in buffered water were equal to those of ERY, with low values of ∼0.02 and a slight increase to ∼0.1 in micellar media, the value of which was still small. The quantum yields of singlet oxygen of all xanthenes investigated were high in micellar systems and similar to each other, independent of the alkyl group (0.6–0.7). ERYDEC showed low ΦΔO21 of 0.38 in buffered water due to the self-aggregation process, but high values in micellar systems. These results in micelles are very important for formulated medications in photodynamic therapy and photodynamic inactivation of microorganisms. Ester derivatives of erythrosin show a potential as photosensitizers in photodynamic clinical applications, especially those formulated with biocompatible surfactants, such as polymeric pluronics.

Development, characterization, and photocytotoxicity assessment on human melanoma of chloroaluminum phthalocyanine nanocapsules

In this work we have developed nanocapsules containing chloroaluminum phthalocyanine (ClAlPc) and assessed their phototoxic action on WM1552C, WM278, and WM1617 human melanoma cell lines. The ClAlPc-loaded nanocapsules were prepared by the nanoprecipitation method and optimized by means of a 23 full factorial design. The ClAlPc nanocapsules were characterized by particle size and distribution, zeta potential, morphology, encapsulation efficiency, singlet oxygen production, stability, and phototoxic action on melanoma cells. Both the development and optimization studies revealed that stable colloidal formulations could be obtained by using 1.75% (w/v) soybean lecithin, 1.25% (w/v) Poloxamer 188, 2.5% (v/v) soybean oil, and 0.75% (w/v) poly(D,L-lactide-co-glycolide). The nanocapsules had a mean diameter of 230nm, homogeneous size distribution (polydispersity index<0.3), and negative zeta potential (about −30mV). Their morphology was spherical, with evident polymer membrane coating droplet. The encapsulation efficiency was 70%, as expected for hydrophobic drugs, and the nanoencapsulated ClAlPc was able to produce high singlet oxygen quantum yield. ClAlPc nanocapsules exhibited good physical stability over a 12-month period. WM1552C primary melanoma cells were more sensitive (p<0.05) to the phototoxic effect elicited by ClAlPc nanocapsules (0.3μgml−1) under light irradiation at 20mJcm−2. On the other hand, the cell survival percentage for all the melanoma cell lines treated with the highest light dose (150mJcm−2) was lower than 10%. In summary, ClAlPc nanoencapsulation could enable application of this hydrophobic photosensitizer in the treatment of malignant melanoma with the use of both low sensitizer drug concentration and light dose.

Novel phthalocyanine and PEG-methacrylates based temperature-responsive polymers for targeted photodynamic therapy

A novel multi-targeting nanocarrier (SiPc-polymer) for photodynamic therapy (PDT) has been successfully polymerized via the incorporation of silicon(IV) phthalocyanine dichloride (SiPcCl2) to the thermoresponsive PEG-methacrylates based polymers. The resulting SiPc-polymer was characterized by 1H NMR spectroscopy, GPC, UV-Vis and elemental analysis. The lower critical solution temperature (LCST) of the SiPc-polymer can be easily controlled via changing the ratio of the applied monomers, di(ethylene glycol) methyl ether methacrylate (DEGMEMA), oligo(ethylene glycol) methyl ether methacrylate (OEGMEMA, Mw = 475 g mol−1) and 2-hydroxyethyl methacrylate (HEMA). The synthesized polymers assemble into nanoparticles (70 nm) in aqueous solution, which normally exhibits permeation and retention (EPR) effects, the thermo-responsive features provide the possibility to selectively accumulate at a maligned tissue site upon mild heating and high singlet oxygen quantum yields (ΦΔ = 0.55) are obtained which guarantee the controlled liberation of reactive oxygen species upon light irradiation. This provides a simple way to synthesize a multi-targeting drug carrier system for PDT.

Water-soluble non-aggregating zinc phthalocyanine and in vitro studies for photodynamic therapy

Newly synthesized zinc phthalocyanine bearing sixteen quaternized imidazolyl moieties on the periphery displays high water-solubility, lack of aggregation and high singlet oxygen quantum yield in water (ΦΔ > 0.33). The in vitro tests indicated excellent anticancer photodynamic activity (EC50 = 36.7 nM) and low dark toxicity to non-cancerous cells (TC50 = 395 μM).

Thienopyrrole-expanded BODIPY as a potential NIR photosensitizer for photodynamic therapy

The synthesis and characterization of a highly photostable bromo-substituted BODIPY dye (I) fused-ring-expanded with thienopyrrole moieties is reported. The results of MTT assays and flow cytometric analyses in living HeLa cells demonstrate that I has a high singlet oxygen quantum yield (ΦΔ = 0.63) and exhibits photocytotoxicity upon irradiation in the NIR region making it potentially suitable for use in PDT.

Photophysical Properties and Singlet Oxygen Generation of Three Sets of Halogenated Corroles

The luminescence, excited-state absorption, and singlet oxygen generation measurements were performed on three kinds of halogenated corroles: monohydroxyl halogenated corroles (Corrole-F, Corrole-Cl, Corrole-I), peripherally fluorine-substituted corroles (F0, F5, F10, F15), and gallium complexes (F10-Ga, F15-Ga). The fluorescence intensities progressively decrease whereas the triplet quantum yields, oxygen quenching rates, and singlet oxygen quantum yields increase with the increasing of the monohydroxyl halogen atomic weight. Replacing hydrogen atoms of meso-phenyl groups with fluorine atoms induces the blue-shifts of the emission spectra, higher triplet quantum yield, and smaller oxygen quenching rates. Of all peripherally fluorine-substituted corroles, F10 exhibited the highest singlet oxygen quantum yield. In comparison with the free base corroles, both gallium corrole complexes display much stronger fluorescence with the large blue-shifts of emission peaks and slightly higher triplet quantum yields but smaller oxygen quenching rates and singlet oxygen quantum yields. The reasons for the different photophysical behaviors of these corroles are discussed.