High Singlet Oxygen Quantum Yield Research Articles

Photodynamic Antitumor and Antimicrobial Activities of Free-Base Tetra(4-methylthiolphenyl)chlorin and Its Tin(IV) Complex.

Meso-tetra(4-methylthiolphenyl)chlorin (3) and its Sn(IV) complex (3-Sn) have been synthesized and characterized. The heavy atom effects of the Sn(IV) ion and sulfur atoms result in relatively high singlet oxygen quantum yield values of 0.40 and 0.48. The photodynamic activities against MCF-7 breast cancer cells were determined through irradiation with a Thorlabs 660 nm LED for 30 min (280 mW.cm-2). IC50 values of 7.8 and 3.9 μM were obtained, respectively. 3-Sn was found to have significant photodynamic antimicrobial activity against both gram-(+) S. aureus and gram-(-) E. coli bacteria upon irradiation with a Thorlabs 660 nm LED for 75 min.

NIR-I region absorbing halogenated phenylamino zinc (II) phthalocyanines: Synthesis and photophysical properties

NIR-I region absorbing dyes with higher tissue penetration, lower auto-fluorescence, minimum photodamage to living tissues, and higher detection sensitivity are attracted great interesting in biological applications. In this paper, three novel NIR I absorbing halogenated phenylamino zinc (II) phthalocyanines have been firstly synthesized through a simple and practical method. They were obtained by condensation of corresponding halogenated phenylamino phthalonitriles. Halogenated phenylamino phthalonitriles were prepared by direct amination of halogenated boronic acids with nitro-phthalonitriles through a reductive molybdenum catalyzed method. The UV/Vis and fluorescence spectra of three halogenated phenylamino zinc phthalocyanines are within NIR-I region because of electron-donating conjugation effect of amine groups. In addition, the effect of substitution terminal halogen atoms as well as α/β substitution position on the UV/Vis and fluorescence spectra of three phthalocyanines were compared. Of three phthalocyanines, 3-BrZnPc with bromo-phenylamino substitution at α position possessed the longest Q-band absorption at 767 nm and fluorescence emission wavelength at 785 nm as well as the highest singlet oxygen quantum yield.

Cobalt(III) Complexes for Light-Activated Delivery of Acetylacetonate-BODIPY, Cellular Imaging, and Photodynamic Therapy.

Cobalt(III) complexes [Co(TPA)(L1)](ClO4)2 (1), [Co(4-COOH-TPA)(L1)](ClO4)2 (2), [Co(TPA)(L2)]Cl2 (3), and [Co(4-COOH-TPA)(L2)]Cl2 (4) having acetylacetonate-linked boron-dipyrromethene ligands (L1, acac-BODIPY; L2, acac-diiodo-BODIPY) were prepared and characterized, and their utility as bioimaging and phototherapeutic agents was evaluated (TPA, tris-(2-pyridylmethyl)amine; 4-COOH-TPA, 2-((bis-(2-pyridylmethyl)amino)methyl)isonicotinic acid). HL1, HL2, and complex 1 were structurally characterized by X-ray crystallography. Complexes 1 and 2 on photoactivation or in a reducing environment (excess GSH, ascorbic acid, and 3-mercaptopropionic acid) released the acac-BODIPY ligand. They exhibited strong absorbance near 501 nm (ε ∼ (5.2-5.8) × 104 M-1 cm-1) and emission bands near 513 nm (ΦF ∼ 0.13, λex = 490 nm) in dimethyl sulfoxide (DMSO). Complexes 3 and 4 with absorption maxima at ∼536 and ∼538 nm (ε ∼ (1.2-1.8) × 104 M-1 cm-1), respectively, afforded high singlet oxygen quantum yield (ΦΔ ∼ 0.79) in DMSO. Complexes 1-4 showed Co(III)-Co(II) redox responses near -0.2 V versus saturated calomel electrode (SCE) in dimethylformamide (DMF)-0.1 M tetrabutylammonium perchlorate (TBAP). The photocleavage of pUC19 DNA by complex 4 revealed the formation of both singlet oxygen and superoxide anion radicals as the reactive oxygen species (ROS). Confocal fluorescence microscopy showed the selective accumulation of complex 1 in the endoplasmic reticulum (ER) in A-549 cells. Complex 4 exhibited a high phototherapeutic index value (PI > 7000) in HeLa cancer cells (IC50 ∼ 0.007 μM in visible light of 400-700 nm, total dose ∼5 J cm-2). The ancillary ligands in the complexes demonstrated a structure-activity relationship and modulated the Co(III)-Co(II) redox potential, the complex solubility, acac-BODIPY ligand release kinetics, and phototherapeutic efficacy.

Metallo-phthalocyanines containing triazole substituents: Synthesis, spectroscopic and photophysicochemical properties

Magnesium(II) (4), lead(II) (5) and zinc(II) (6) phthalocyanines were prepared. The structures of 4–6 were confirmed by the spectroscopic characterization such as FT-IR, 1H-NMR, MALDI-TOF mass, UV-vis and fluorescence spectral data. The aggregation behavior of the triazole substituted phthalocyanines (4–6) was investigated in different solvents and no aggregation was observed. The photophysicochemical properties of 4–6 were investigated in DMSO. The photophysical and photochemical behaviors varied depending on the type of metal in the center of phthalocyanine. The zinc(II) phthalocyanine 6 showed the highest singlet oxygen quantum yield and the highest photostability. The magnesium(II) phthalocyanine 4 exhibited the highest fluorescence quantum yield. The zinc(II) phthalocyanine 6 has good photosensitizer performance due to its high singlet oxygen generation ability, high photostability and formation of non-aggregated species.

Light-driven antimicrobial therapy of palladium porphyrins and their chitosan immobilization derivatives and their photophysical-chemical properties

The emergence of antimicrobial resistance has made the development of photodynamic therapy (PDT) related applications essential, since microorganisms can not form resistance to this method. Porphyrins are well-known photosensitizers for PDT related applications. Thus, the present study outlines the synthesis, characterization and evaluation of the utility of palladium porphyrins and their chitosan inclusion complexes as photosensitizer dye in photodynamic antimicrobial therapy (PACT). Before in vitro cell studies, the photophysical-chemical studies of all obtained structures were performed in solution. It was observed that the immobilization of the porphyrins into the chitosan influenced the photophysical-chemical and PACT activity properties. The determined fluorescence quantum yield was very low, in the range of 0.007–0.028 for all samples indicating the efficient triplet state population to cause high singlet oxygen quantum yield (ΦΔ). The measured ΦΔ values were in the range of 0.51–0.61 for the porphyrins and 0.53–0.66 for porphyrin chitosan immobilization complexes. Our results demonstrate that the PACT activity of cationic porphyrin (P3) and its chitosan immobilization form (P3-Ct) were more efficient in decreasing the number of viable cells up to 100% in vitro.

Effect of Substituents on the Photodynamic Action of Anthraquinones: EPR, Computational and In Vitro Studies.

Anthraquinone class of compounds possesses a broad spectrum of therapeutic applications. Cancer cell targeting ability, together with photogeneration of reactive oxygen species, renders anthraquinones an interesting class of photosensitizers for photodynamic therapy (PDT). Screening of newer compounds for better singlet oxygen generation is of current interest to improve the practical usability in PDT. In this study, we investigate the photodynamic activity of nine commercially available anthraquinones, using EPR spectroscopy and computational techniques, to identify the role of substituents on singlet oxygen yield. Three anthraquinone derivatives, 1,5-diaminoanthraquinone, 15-dihydroxyanthraquinone and 1,2,7-trihydroxyanthraquinone, showed highest singlet oxygen quantum yield (0.21, 0.18 and 0.15, respectively) relative to Rose Bengal. Time-dependent density functional theory calculations indicate the singlet oxygen quantum yield of anthraquinones inversely correlate well with the excited singlet-triplet (S1-T1) energy gap. Electron-donating substituents present at positions 1, 2 and 5 of anthraquinone seem to reduce the S1-T1 energy gap, facilitating inter-system crossing and the production of singlet oxygen. This would greatly aid in the design of newer anthraquinone-based photosensitizers. This study also highlights the suitability of 1,5-diaminoanthraquinone for PDT applications as demonstrated by invitro experiments of photoinduced DNA cleavage and photocytotoxicity in Dalton's lymphoma ascites.

Synthesis and in vitro biological evaluation of novel water‐soluble porphyrin complexes for cancer photodynamic therapy

AbstractIn this study, we report the synthesis and biological evaluation of four novel cationic porphyrins (named as P1, P2, ZnP2, and CuP2) with potential as a photodynamic therapeutic agent. MTT experiments proved that P1, P2, and ZnP2 have high light toxicity and low dark toxicity for A549, H‐1975, and HepG2 cell lines. In addition, due to the specific targeting of porphyrin, there was only a weak toxicity to Hs 578Bst normal breast cancer cells. The study further confirmed the intracellular generation of reactive oxygen species (ROS) under light irradiation and ZnP2 could be effectively internalized by cells and also indicated that the photodynamic therapy effect achieved by ZnP2 and light irradiation can cause significant cell apoptosis. High relative singlet oxygen quantum yield and excellent phototoxicity ensure the optimal photosensitizer ZnP2 becomes potential candidates for photodynamic therapy drugs. Our results disclosed that the cationic porphyrin complexes used photodynamic therapy for the development of new and useful metal anticancer photosensitizer provide a strong platform.

Injectable photosensitizing supramolecular hydrogels: A robust physically cross-linked system based on polyvinyl alcohol/chitosan/tannic acid with self-healing and antioxidant properties

The development of injectable and photosensitizing supramolecular hydrogels has proved to be a challenging and interesting task. In this study, N, N′-di-(L-alanine)-3,4,9,10-perylene tetracarboxylic diimide (PDI-Ala), as a photosensitizing agent, was incorporated into single (PVA-CS-PDI/TA) and double cross-linked (PVA-CS-PDI/TA/Fe (III)) hydrogels formed by poly (vinyl alcohol) (PVA), chitosan (CS), and tannic acid (TA) through a freeze-thawing method based on non-covalent interaction (hydrogen bonding and metal coordination). TA molecules act as cross-linkers to connect polymer chains through multiple hydrogen bonds and cross-link them using coordinate bonds in the presence of Fe (III) ions. The double cross-linked hydrogels had a higher singlet oxygen quantum yield than single cross-linked hydrogels under 660 nm laser irradiation, indicating those that could be more efficient in photodynamic therapy (PDT). Supramolecular hydrogels with interconnected porous morphologies exhibited mechanical strength, injectability, self-healing and shear-thinning capabilities, antioxidant and antibacterial properties. Additionally, the supramolecular photosensitizing hydrogels showed excellent biocompatibility without showing evident cytotoxicity and hemolysis in vitro. This study presents a straightforward and cost-effective approach to prepare multifunctional physical cross-linking supramolecular hydrogels, appropriate for large-scale preparation, which shows great potential in biomedical applications such as PDT and wound dressings.

A simple route toward triplet-forming thionated BODIPY-based photosensitizers

Thiobases or sulfur-substituted nucleobases have been developed and recognized as prospective class of heavy-atom-free photosensitizer for photodynamic therapy due to their appealing phototherapeutic properties. In this work, we have prepared the thionated BODIPY analogues by replacing oxygen with sulfur atom at exocyclic carbonyl group, which display red-shifted absorption band, remarkable fluorescence quenching and high singlet oxygen quantum yield as well as excellent photostability. Sulfur substitution stabilizes the LUMO level and destabilized the HOMO, and thus reduces the energy gap and shift the absorption to long wavelength. The replacement of O by S-atom is essential for the enhancement of the intersystem crossing from the singlet excited state to the reactive triplet state. DFT calculations revealed that large spin-orbit coupling (SOC) could be responsible for the efficient population of the triplet state. In addition, the thionated BODIPY efficiently generates the intracellular reactive oxygen species (ROS) with low cytotoxicity. These studies demonstrate that the thionated BODIPY analogue is potentially suitable for use as a photosensitizer.

Bichromophoric ruthenium(II) bis-terpyridine-BODIPY based photosensitizers for cellular imaging and photodynamic therapy.

Two multichromophoric homoleptic ruthenium(II) complexes [Ru(tpy-BODIPY)2]Cl2 (complexes 1 and 2, tpy = 4-phenyl-2,2:6,2-terpyridine, BODIPY = boron-dipyrromethene) were prepared, characterized and their phototherapeutic activity and bioimaging properties were studied. The complexes having structural similarity differ only by a phenylethynyl linker, and its overall influence on their physicochemical and photobiological behavior was evaluated. The terpyridine-BODIPY ligand L1 was structurally characterized by X-ray crystallography. The complexes showed intense absorption near 500 nm (ε: ∼1.5 × 105 M-1 cm-1 in DMSO), have a high singlet oxygen quantum yield (ΦΔ: ∼0.6 in DMSO), and displayed low photobleaching thus making them suitable for PDT applications. The complexes showed high DNA binding affinity and induced DNA damage on light activation via multiple types of ROS production. Confocal laser scanning microscopy experiments revealed their incorporation in the cancer cells and complex 1 predominantly accumulated in lysosomes. The complexes displayed a significant PDT effect in cancerous cells with visible light activation with a high photocytotoxicity index (PI) value in HeLa cells. Both type-I and type-II photosensitization processes were involved in the PDT effect. The photodynamic action of complex 2 initiated cellular apoptosis. Finally, their diagnostic potential was evaluated against clinically relevant 3D multicellular tumor spheroids (MCTs).

Multifunctional nanoplatform based on g-C3N4, loaded with MnO2 and CuS nanoparticals for oxygen self-generation photodynamic/photothermal synergistic therapy

Photodynamic therapy (PDT) and photothermal therapy (PTT) are both promising therapeutic approaches for cancer. Unfortunately, the anticancer efficiency of PDT is restricted by the hypoxic tumor microenvironment and the performance of the photosensitizer (PS) while the efficiency of PTT is limited by the penetration depth of NIR light, making it difficult to further improve the efficiency of the treatment. In this paper, we strategically proposed a multifunctional nano-platform based on g-C3N4 and loaded with CuS and MnO2 nanoparticals. Interestingly, the obtained F127@CNs-CuS/MnO2 nano-platform with high singlet oxygen quantum yield and excellent photothermal performance were used in synergistic PTT and PDT therapy to cope with the limitation of single mode cancer treatment under irradiation and has greatly improved the treatment effect. Additionally, MnO2 nanoparticles loaded on the CNs surface could not only generate oxygen to ameliorate hypoxia in the tumor environment by reacting with H2O2 in tumor cells, but also react with the over-expressed reduced glutathione (GSH) in cancer cells to further improve the synergistic therapeutic effect. In the in vitro hepatocarcinoma cell inactivation experiment, the maximum cell inactivation efficiency of the PDT, PTT and PDT/PTT synergistic treatment group reached at 65% (F127@CNs-MnO2), 69.2% (CNs-MnO2) and 88.6% (F127@CNs-MnO2) respectively, which means that the F127@CNs-CuS/MnO2-mediated PTT/PDT synergy anticancer treatment was more effective than single mode therapy. In summary, the innovative multifunctional nanoplatform F127@CNs-CuS/MnO2 used for synergistic PTT and PDT treatment has greatly improved the inactivation efficiency of cancer cells and has provided a new scheme for the treatment of hypoxic tumors.

Synthesis and photophysical properties of metal complexes of curcumin dyes: Solvatochromism, acidochromism, and photoactivity

Curcumin and its dyes have attracted attention due to their environment-sensitivity and optical properties. However, the free molecule has low photoactivity, which is a limitation for use in photodynamic therapy. To overcome this limitation, we proposed the chelation of a D-π-A-π-D curcumin dye (1) with the metals Cu (II) and Pd (II). The photophysical properties of the curcumin dyes were investigated in different solvents, using UV–vis spectroscopy and time-resolved/steady-state fluorescence techniques. In our results, all curcumin dyes exhibited a positive solvatochromism from non-polar to polar solvents, with the Stokes’ shift in the range of 1895–4970 cm−1. The acidochromism studies were performed in chloroform solution and TLC plates using trifluoroacetic acid (TFA). The results exhibited a negative acidochromism and fluorescence quenching upon gradual addition of TFA, demonstrating reversibility upon addition of triethylamine (TEA). The main mechanism which influences the solvatochromism/acidochromism is the ICT system and fluorescence lifetime decays exhibited mono-exponential fit for aprotic solvents and bi-exponential fit for protic solvents (EtOH and MeOH). Compared to the curcumin ligand (1), the metal complexes (1a-b) exhibited higher singlet oxygen quantum yields (ΦΔ = 0.36 and 0.54, respectively). The in vitro antimicrobial photoactivity of the compounds was evaluated against six different microorganisms. The results showed that the metal complexes (1a-b) exhibited both antileishmanial (MIC = 2.29 μM against Leishmania amazonensis promastigotes) and antifungal (IC50 = 10 μM against Sporothrix brasiliensis yeasts) activities, while the ligand showed no activity, suggesting the chelation with the metals Cu (II) and Pd (II) may improve its photoactivity.

The First Selenoanhydride in the Series of Chlorophyll a Derivatives, Its Stability and Photoinduced Cytotoxicity.

In this work, we obtained the first selenium-containing chlorin with a chalcogen atom in exlocycle E. It was shown that the spectral properties were preserved in the target compound and the stability increased at two different pH values, in comparison with the starting purpurin-18. The derivatives have sufficiently high fluorescence and singlet oxygen quantum yields. The photoinduced cytotoxicity of sulfur- and selenium-anhydrides of chlorin p6 studied for the first time in vitro on the S37 cell line was found to be two times higher that of purpurin-18 and purpurinimide studied previously. Moreover, the dark cytotoxicity increased four-fold in comparison with the latter compounds. Apparently, the increase in the dark cytotoxicity is due to the interaction of the pigments studied with sulfur- and selenium-containing endogenous intracellular compounds. Intracellular distributions of thioanhydride and selenoanhydride chlorin p6 in S37 cells were shown in cytoplasm by diffusion distribution. The intracellular concentration of the sulfur derivative turned out to be higher and, as a consequence, its photoinduced cytotoxicity was higher as well.

Highly Efficient Multifunctional Organic Photosensitizer with Aggregation-Induced Emission for In Vivo Bioimaging and Photodynamic Therapy.

Photosensitizers play a critical role in photodynamic therapy (PDT). Multifunctional organic nanoparticles (NPs) that possess bright fluorescence in aggregates, high singlet oxygen (1O2) quantum yield, near-infrared (NIR) absorption and emission, large Stokes shift, two-photon bioimaging, specific organelle targeting, high PDT efficiency, as well as good biocompatibility and photostability are ideal candidate photosensitizers for image-guided PDT. Due to its enhanced fluorescence and high 1O2 generation efficiency in aggregate states, photosensitizers with aggregation-induced emission (AIE) characteristics have attracted increasing interest in PDT. In this study, a new AIE-active Schiff base 5-(((5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)methylene)amino)-3-methylthiophene-2,4-dicarbonitrile (TBTDC) based on a D-A-π-A skeleton has been designed and synthesized, and it can be readily encapsulated by Pluronic F-127 to form uniform nanoparticles. TBTDC NPs exhibit bright NIR emission at 825 nm with a Stokes shift up to 300 nm, impressive two-photon bioimaging capability with tissue penetration deep into 300 μm, high 1O2 generation quantum yield (0.552), specific targeting to lysosome, as well as good biocompatibility and photostability. Furthermore, TBTDC NPs present remarkable cytotoxicity for tumor cells and suppression of tumor growth in nude mice through reactive oxygen species generation upon white light irradiation. These results reveal that TBTDC NPs have great potential to become excellent candidates for multifunctional organic photosensitizers for two-photon bioimaging and image-guided PDT and are promising in future clinical applications.

Modulation of fluorescent protein chromophore for photodynamic therapy and two-photon fluorescent imaging in living cells

The green fluorescent protein (GFP) chromophore has been widely applied as a biological marker or viscosity sensor. However, modulation of GFP chromophore for photodynamic therapy (PDT) has rarely been reported. Inspired by this, through the unique phenothiazine-anchored strategy, a near-infrared emission photosensitizer Lys-PtzFP was designed and synthesized to achieve this process. The maximum absorption wavelength of Lys-PtzFP was 460 nm and the corresponding molar extinction coefficient was 6.60 × 104 M−1 cm−1 in MeOH. The maximum emission wavelengths of Lys-PtzFP was at 725 nm. The photosensitizer Lys-PtzFP showed a high singlet oxygen quantum yield (ΦΔ = 0.42) and low fluorescence quantum yield (φF = 0.002) in MeOH. Besides, Lys-PtzFP possessed high specificity for lysosomes with negligible dark cytotoxicity (MTT assay >94.6%), good photostability and low half-maximal inhibitory concentration (IC50) of 0.93 μM. Finally, the intracellular photodynamic therapy experiments revealed that Lys-PtzFP can produce singlet oxygen in lysosomes and induce apoptosis under irradiation. In conclusion, Lys-PtzFP could be a promising photosensitizer for PDT and two-photon imaging applications. This type of photosensitizer can inspire the development of new photosensitizers for further explore highly efficient PDT.

Porpholactam-cinnamaldehyde conjugates for promoting ROS generation in photodynamic therapy

Photodynamic therapy (PDT) is a non-invasive method for cancer treatment that relies on the generation of excess reactive oxygen species (ROS), upon excitation of photosensitizer (PS), to eradicate tumor cells. However, the overexpress of endogenous antioxidants in tumor cells will eliminate the ROS and restrict the therapeutic efficacy of PDT. Herein, a novel type of PS was developed by conjugating cinnamaldehyde (CA), a kind of oxidative stress amplified agent, with porpholactam through a hydrazone bond. The new PS retains the photophysical properties of porpholactam, which displays high singlet oxygen quantum yield for the PDT function. The results of in vitro experiments performed including ROS assay and the cytotoxicity in cancer cells suggest that the rational design of the novel porpholactam-CA derivatives result in enhanced ROS generation upon irradiation, providing a possible approach to achieve enhanced therapeutic effects in PDT.

Asymmetricallymeso-substituted porphyrin derivative containing the triazole group: Synthesis, characterization and photo-physicochemical properties

In this study, a novel asymmetrically meso-substituted AB3porphyrins derivative including one triazole group to enhance the anticancer activity of the molecule and three bromophenyl groups to improve photochemical properties has been synthesized and characterized. Our objectives were to generate a system with triazole and bromophenyl groups that enhance the singlet oxygen generation and exhibits an anti-cancer effect. Therefore, photophysical and photochemical properties of this asymmetric porphyrin derivative (AB[Formula: see text] and the symmetric derivative (B[Formula: see text] were investigated in THF. The substituent effect on fluorescence quantum yield and singlet oxygen generation was evaluated for efficiency in photodynamic therapy (PDT) as a photosensitizer. The molecules exhibited no aggregation tendency, solubility in common organic solvents and high singlet oxygen quantum yield in THF therefore these favorable properties make them good candidates as a photosensitizer for PDT.

Photophysicochemical properties of [Tetrakis 6-(tert-butyl)-2,3-dihydrobenzo [b] [1,4] dioxine) phthalocyaninato] In(III) and Zn(II) with very high singlet oxygen quantum yield

Synthesis and photophysicochemical properties of [tetrakis 6-(tert-butyl)-2,3-dihydrobenzo [b] [1,4] dioxine) phthalocyaninato] In(III) (InPc-4) and [tetrakis 6-(tert-butyl)-2,3-dihydrobenzo [b] [1,4] dioxine) phthalocyaninato] Zn(II) (ZnPc-5) containing 4-tert-butylcatechol at the peripheral positions are synthesised for application as photosensitisers in photodynamic therapy (PDT). Fluorescence quantum yield, singlet oxygen quantum yield and photodegradation quantum yield were determined for each complex. High singlet oxygen quantum yield of 0.84 and 0.86 (in THF) were obtained for InPc-4 and ZnPc-5, respectively. Density functional theory (DFT) and time dependent density functional theory (TDDFT) were carried out to rationalise the experimental results.

Analysis of the Isotopic Purity of D2O with the Characteristic NIR-II Phosphorescence of Singlet Oxygen from a Photostable Polythiophene Photosensitizer.

D2O plays important roles in a variety of fields (such as the nuclear industry and bioorganic analysis), and thus its isotopic purity (H2O contents) is highly concerned. Due to its highly similar physical properties to H2O and large excess amounts of H2O over D2O, it is challenging to distinguish D2O from H2O. On the basis of the characteristic NIR-II phosphorescence of singlet oxygen (1O2), and the fact that H2O is a more efficient quencher for 1O2 than D2O, here, we proposed to simply use the 1275 nm emission of 1O2 for the analysis of the isotopic purity of D2O. In normal cases (a xenon lamp for excitation), such steady-state emission is extremely weak for valid analytical applications, we thus employed laser excitation for intensification. To this goal, a series of photosensitizers were screened, and eventually polythiophene PT10 was selected with high singlet oxygen quantum yield (ΦΔ = 0.51), high H2O/D2O contrast, and excellent photostability. Upon excitation with a 445 nm laser, a limit of detection (LOD, 3σ) of 0.1% for H2O in D2O was achieved. The accuracy of the proposed method was verified by the analysis of the isotopic purity of several D2O samples (with randomly added H2O). More interestingly, the hygroscopicity of D2O was sensitively monitored with the proposed probe in a real-time manner; the results of which are important for strengthening the care of D2O storage and the importance of humidity control during related investigations. Besides D2O isotopic purity evaluation, this work also indicated the potential usefulness of the NIR-II emission of singlet oxygen in future analytical detection.

A hydrogen peroxide responsive resorufin-based phototheranostic agent for selective treatment of cancer cells

Enhanced selectivity towards cancer cells is one of the most essential features sought in new generation photodynamic therapy (PDT) agents in order to minimize the side effects on healthy cells and to improve the efficacy of the treatment. In this direction, one promising approach is to design activatable photosensitizers, which tend to stay in an OFF state and get activated only in cancer cells with tumor-associated stimuli. Based on this idea, herein we introduced a hydrogen peroxide (H2O2) activatable iodinated resorufin (RR-1) as a red-shifted, water soluble and cancer cell selective photosensitizer. RR-1 exhibited high singlet oxygen quantum yield in aqueous solutions upon reacting with H2O2 and induced selective photocytotoxicity in colorectal (HCT-116) and triple negative breast (MDA MB-231) cancer cells, which contain high level of reactive oxygen species (ROS). Additionally, fluorescence signal of the iodo-resorufin core was restored upon cleavage of the cage unit in these cancer cells. In contrast, very low photocytotoxicity and negligible fluorescence enhancement were observed in normal fibroblast (NIH-3T3) cells. RR-1 not only marks the first example of a H2O2 activatable resorufin-based photosensitizer but also represents the first ever resorufin-based theranostic agent. We anticipate that iodo-resorufin scaffold can be easily modified with different masking units towards realization of highly selective and efficient phototheranostic agents for treatment of various cancer cells.