Enhancing the Photosensitivity of Hypocrellin A by Perylene Diimide Metallacage‑Based Host–Guest Complexation for Photodynamic Therapy

The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy.Here,we report two perylene diimide-based metallacages that can form stable host–guest complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers(hypocrellin A).Such host–guest complexation not only prevents the aggregation of photosensitizers in aqueous environments,but also offers fluorescence resonance energy transfer(FRET)from the metallacage to the photosensitizers to further improve the singlet oxygen generation(Φ_(Δ)=0.66).The complexes are further assembled with amphiphilic polymers,forming nanoparticles with improved stability for anticancer study.Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation,showing great potential for cancer photodynamic therapy.This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host–guest complexation-based FRET,which will open a new avenue for host–guest chemistry-based supramolecular theranostics.

Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

Reduction of photodynamic damage of blood vessels in the protected region by(–)-epigallocatechin gallate

Photodynamic therapy(PDT)has been increasingly used in the clinical treatment of neoplastic,inflammatory and infectious skin diseases.However,the generation of reactive oxygen species(ROS)may induce undesired side effects in normal tissue surrounding the treatment lesion,which is a big challenge for the clinical application of PDT.To date,(–)-Epigallocatechin gallate(EGCG)has been widely proposed as an antiangiogenic and antitumor agent for the protection of normal tissue from ROS-mediated oxidative damage.This study evaluates the regulation ability of EGCG for photodynamic damage of blood vessels during hematoporphyrin monomethyl ether(Hemoporfin)-mediated PDT.The quenching rate constants of EGCG for the triplet-state Hemoporfin and photosensitized 1O2 generation are determined to be 6.8×10^(8)M^(−1)S^(−1),respectively.The vasoconstriction of blood vessels in the protected region treated with EGCG hydrogel after PDT is lower than that of the control region treated with pure hydrogel,suggesting an efficiently reduced photodamage of Hemoporfin for blood vessels treated with EGCG.This study indicates that EGCG is an efficient quencher for triplet-state Hemoporfin and 1O2,and EGCG could be potentially used to reduce the undesired photodamage of normal tissue in clinical PDT.

Heterogeneous catalytic activation of peroxymonosulfate for efficient degradation of organic pollutants by magnetic Cu^0/Fe_3O_4 submicron composites

Magnetic Cu^0/Fe3O4 submicron composites were prepared using a hydrothermal method and used as heterogeneous catalysts for the activation of peroxymonosulfate（PMS） and the degradation of organic pollutants.The as-prepared magnetic Cu^0/Fe3O4 submicron composites were composed of Cu^0 and Fe3O4 crystals and had an average size of approximately 220 nm.The Cu^0/Fe3O4 composites could efficiently catalyze the activation of PMS to generate singlet oxygen,and thus induced the rapid degradation of rhodamine B,methylene blue,orange Ⅱ,phenol and 4-chlorophenol.The use of0.1 g/L of the Cu^0/Fe3O4 composites induced the complete removal of rhodamine B（20 μmol/L） in15 min,methylene blue（20 μmol/L） in 5 min,orange Ⅱ（20 μmol/L） in 10 min,phenol（0.1mmol/L） in 30 min and 4-chlorophenol（0.1 mmol/L） in 15 min with an initial pH value of 7.0 and a PMS concentration of 0.5 mmol/L.The total organic carbon（TOC） removal higher than 85%for all of these five pollutants was obtained in 30 min when the PMS concentration was 2.5 mmol/L.The rate of degradation was considerably higher than that obtained with Cu^0 or Fe3O4 particles alone.The enhanced catalytic activity of the Cu^0/Fe3O4 composites in the activation of PMS was attributed to the synergistic effect of the Cu^0 and Fe3O4 crystals in the composites.Singlet oxygen was identified as the primary reactive oxygen species responsible for pollutant degradation by electron spin resonance and radical quenching experiments.A possible mechanism for the activation of PMS by Cu^0/Fe3O4 composites is proposed as electron transfer from the organic pollutants to PMS induces the activation of PMS to generate ^1O2,which induces the degradation of the organic pollutants.As a magnetic catalyst,the Cu^0/Fe3O4 composites were easily recovered by magnetic separation,and exhibited excellent stability over five successive degradation cycles.The present study provides a facile and green heterogeneous catalysis method for the oxidative removal of organic pollutants.

Photoactivated Activities on Spodoptera litura Cell, Singlet Oxygen and Photostability of Photosensitizers

[Objective ]The aim of this study was to improve the photostability of pho-tosensitizers. [Method] 2,5-Diphenylthiophene and 2,5-dithienylethynylthiophene were synthesized by replacing thiophene rings of α-terthienyl （α-T） with benzene rings. Photoactivated activities on Spodoptera litura （SL） cells, singlet oxygen with UV and photostability of photosensitizers were investigated. [Result] The cytotoxicity of pho-tosensitizer 2,5-diphenylthiophene on SL cells was 0.22 and 0.16 μg/ml after treat-ment for 24 and 48 h, respectively, while that of 2,5-dithienylethynylthiophene on SL cells was 0.06 and 0.04 μg/ml. Singlet oxygen of 2,5-diphenylthiophene and 2,5-dithienylethynylthiophene was 1.047 5, 1.529 4 μg/mmol under UV, respectively. Degradation dynamic equations of 2,5-diphenylthiophene and 2,5-dithienylethynylthio-phene in methanol were Ct= 5.227 1e-0.006 1t, Ct= 5.084 2e-0.097 3t and half life was 111.79, 7.12 h. [Conclusion] Photosensitizer 2,5-diphenylthiophene has high singlet oxygen production ability, and high photoactivated cytotoxicity on SL cells under UV. Moreover, 2,5-diphenylthiophene has overcome the deficiency of photoactivated in-secticides, which is not applied directly in field because it degrades quickly in the environment.

Structure of the Universe

Based on a cosmological model without singularity, a possible structure of the universe is presented. It is proved that there must simultaneously be two sorts of symmetry breaking in the universe. The universe is composed of infinite s-cosmic islands, infinite v-cosmic islands and infinite transition zone. The existing and changing forms of the cosmic islands must be diverse. The cosmological principle holds only approximately within a cosmic island. No information can be exchanged between an s-cosmic island and an adjacent v-cosmic island so that every observer thinks his cosmic island to be the whole universe. It is possible that some cosmic islands are contracting, some cosmic islands are expanding, and other cosmic islands are stable for a time. But the universe as a whole is always invariable and contains all possible existing forms of matter. To give a possible explanation for orphan quasars. To predict some characteristics of contracting large and huge black holes in a cosmic island. The characteristics of the light coming from the contracting huge black holes are that the intensity of the light is huge relatively to their distance, the red shifts are huge, the distribution of the huge red shifts and the orphan quasars are anisotropic, and luminescence spectrum is very wide.

O2（1△g） Deactivation on O2-adsorbed Metal Surfaces

A flow system was set up to measure the quenching probability ~ of O2（1△g） on various O2- adsorbed metal surfaces including Cu, Cr, Ni, and Ag. increased with both the duration of the experiment and the O2（1△g） concentration. After several hours evacuation to a few Pa, γ can return to its original value. A deactivation mechanism of O2（1△g） is suggested by considering first the weak chemisorption of O2（1△g） on the surface adsorption sites, followed by the near resonant energy transfer between the gas phase O2（1△g） and surface O2（1△g）. A phenomenological model in accord with the experimental fact has been proposed together with relevant kinetic equations.

Singlet oxygen synergistic surface-adsorbed hydroxyl radicals for phenol degradation in CoP catalytic photo-Fenton

In recent years,there have been numerous studies on Fenton or Fenton-like reactions mediated by nonfree radicals such as singlet oxygen(1O_(2));however,there are few studies on the synergistic effect of 1O_(2) and free radicals on the degradation of organic molecules,such as phenol in Fenton reaction.In this study,a cocatalyst,CoP,commonly used in photocatalysis was synthesized using a simple two-step method,and a CoP/Fe^(2+)/AM1.5 system was constructed by introducing Fe^(2+)and simulated sunlight(AM1.5)irradiation.The newly constructed CoP/Fe^(2+)/AM1.5 system could effectively degrade various organic pollutants,including dyes,phenols,and antibiotics.Radical quenching experiments and electron paramagnetic resonance detection confirmed that there were three reactive oxygen species(ROS)in the CoP/Fe^(2+)/AM1.5 system,including·OH_(ads),·O_(2)^(-),and 1O_(2).Further,combined with the liquid chromatogram of phenol,its intermediate products,and the fluorescence diagram of o-hydroxybenzoic acid,it can be concluded that a synergistic effect exists between 1O_(2) and the surface-adsorbed·OH_(ads) in the CoP/Fe^(2+)/AM1.5 system.The controllable formation of surface 1O_(2) and·OH_(ads) was achieved through the oxidation(Co^(3+))and reduction(Pδ−)centers exposed on the CoP surface,and the synergistic effect between them results in phenol’s hydroxylation,ring-opening,and degradation.The study of this new mechanism provides a new perspective for revealing the surface interface reaction between ROS and organic pollutants.

Emerging Strategies in Enhancing Singlet Oxygen Generation of Nano-Photosensitizers Toward Advanced Phototherapy

The great promise of photodynamic therapy(PDT) has thrusted the rapid progress of developing highly effective photosensitizers(PS) in killing cancerous cells and bacteria. To mitigate the intrinsic limitations of the classical molecular photosensitizers, researchers have been looking into designing new generation of nanomaterial-based photosensitizers(nano-photosensitizers) with better photostability and higher singlet oxygen generation(SOG) efficiency, and ways of enhancing the performance of existing photosensitizers. In this paper, we review the recent development of nano-photosensitizers and nanoplasmonic strategies to enhance the SOG efficiency for better PDT performance. Firstly, we explain the mechanism of reactive oxygen species generation by classical photosensitizers, followed by a brief discussion on the commercially available photosensitizers and their limitations in PDT. We then introduce three types of new generation nanophotosensitizers that can effectively produce singlet oxygen molecules under visible light illumination, i.e., aggregation-induced emission nanodots, metal nanoclusters (< 2 nm), and carbon dots. Different design approaches to synthesize these nano-photosensitizers were also discussed. To further enhance the SOG rate of nano-photosensitizers, plasmonic strategies on using different types of metal nanoparticles in both colloidal and planar metal-PS systems are reviewed. The key parameters that determine the metal-enhanced SOG(ME-SOG) efficiency and their underlined enhancement mechanism are discussed. Lastly, we highlight the future prospects of these nanoengineering strategies, and discuss how the future development in nanobiotechnology and theoretical simulation could accelerate the design of new photosensitizers and ME-SOG systems for highly effective image-guided photodynamic therapy.

SINGLET OXYGEN QUANTUM YIELDS OF PORPHYRIN-BASED PHOTOSENSITIZERS FOR PHOTODYNAMIC THERAPY

The major cytotoxic agent with most current photosensitizers used in photodynamic therapy(PDT)is widely believed to be singlet oxygen(^(1)O_(2)).Determination of the ^(1)O_(2) quantum yields for porphyrin-based photosensitizers,including hematoporphyrin derivative(HiPorfin),hematoporphyrin monomethyl ether(HMME)and photocarcinorin(PsD-007)in air-saturated dimethylformamide(DMF)solutions were performed by the direct measurement of their near-infrared luminescence.In addition,^(1)O_(2) quencher sodium azide was employed to confirm the ^(1)O_(2) generation from the investigated photosensitizers.The maximal ^(1)O_(2) luminescence occurs at about 1280 nm with full width at half maximum of 30 nm.The ^(1)O_(2) quantum yields were found to be 0.61±0.03,0.60±0.02 and 0.59±0.03 for HiPorfin,HMME and PsD-007,respectively.These results provide that these porphyrin-based photosensitizers produce ^(1)O_(2) under irradiation,which is of significance for the study of their photodynamic action in PDT.

Ag7(MBISA)6 Nanoclusters Conjugated with Quinacrine for FRET-Enhanced Photodynamic Activity under Visible Light Irradiation

Singlet oxygen(1 O2) plays an important role in various applications, such as in the photodynamic therapy(PDT) of cancers,photodynamic inactivation of microorganisms, photo-degradation of toxic compounds, and photo-oxidation in synthetic chemistry. Recently,water-soluble metal nanoclusters(NCs) have been utilized as photosensitizers for the generation of highly reactive 1 O2 because of their high water solubility, low toxicity, and surface functionalizability for targeted substances. In the case of metal NC-based photosensitizers, the photo-physical properties depend on the core size of the NCs and the core/ligand interfacial structures. A wide range of atomically precise gold NCs have been reported; however, reports on the synthesis of atomically precise silver NCs are limited due to the high reactivity and low photostability(i.e., easy oxidation) of Ag NCs. In addition, there have been few reports on what kinds of metal NCs can generate large amounts of 1 O2. In this study, we developed a new one-pot synthesis method of water-soluble Ag7(MBISA)6(MBISA= 2-mercapto-5-benzimidazolesulfonic acid sodium salt) NCs with highly efficient 1 O2 generation ability under the irradiation of white light emitting diodes(LEDs). The molecular formula and purity were determined by electrospray ionization mass spectrometry and gel electrophoresis. To the best of our knowledge, this is the first report on atomically precise thiolate silver clusters(Agn(SR)m) for efficient 1 O2 generation under visible light irradiation. The 1 O2 generation efficiency of Ag7(MBISA)6 NCs was higher than those of the following known water-soluble metal NCs: bovine serum albumin(BSA)-Au25 NCs,BSA-Ag8 NCs, BSA-Ag14 NCs,Ag25(dihydrolipoic acid)14 NCs,Ag35(glutathione)18 NCs,and Ag75(glutathione)40 NCs. The metal NCs examined in this study showed the following order of 1 O2 generation efficiency under white light irradiation: Ag7(MBISA)6 > BSA-Ag14 > Ag75(SG)40 > Ag35(SG)18 >BSA-Au25 >>BSA-Ags(not detected) and Ag2 s(DHLA)14(not detected). For further improving the 1 O2 generation of Ag7(MBISA)6 NCs, we developed a novel fluorescence resonance energy transfer(FRET) system by conjugating Ag7(MBISA)6 NCs with quinacrine(QC)(molar ratio of Ag NCs to QC is 1 : 0.5). We observed the FRET process,from QC to Ag7(MBISA)6 NCs,occurring in the conjugate. That is,the QC works as a donor chromophore,while the Ag NCs work as an acceptor chromophore in the FRET process. The FRET-mediated process caused a 2.3-fold increase in 1 O2 generation compared to that obtained with Ag7(MBISA)6 NCs alone. This study establishes a general and simple strategy for improving the PDT activity of metal NC-based photosensitizers.

Determination of photochemically-generated reactive oxygen species in natural water

Reactive oxygen species （ROS） can be produced by interactions between sunlight and light-absorbing substances in natural water environment. ROS may participate in the indirect photolysis of trace organic pollutants, therefore resulting in changes in their environmental fates and ecological risks in natural water systems. Bisphenol A （BPA）, an endocrine-disrupting chemical, exits widely in natural waters. The photodegradation of BPA promoted by ROS （-OH, 1O2, HO2./O2^-）, which were produced on the excitation of ubiquitous constituents （such as nitrate ion, humic substances and Fe（Ⅲ）-oxalate complexes） in natural water under simulated solar radiation was investigated. Both molecular probe method and electron spin resonance （ESR） test were used for the characterization of the generated ROS. It was found that .OH was photochemically produced in the presence of nitrate ions, humic substances and Fe（Ⅲ）-oxalate complexes and that 102 was produced with the presence of humic substances. The steady-state concentrations of .OH was 1.27×10^-14 mol/L in a nitrate solution, and the second-order rate constant of BPA with ＂OH was 1.01×10^10 L/（mol.s）.

A High Sensitivity Detection Method of Singlet Oxygen and Superoxide Anion

This paper, for the first time, reports a method that can be used as a highly sensitive probe for singlet oxygen (1O2) and superoxide anion (O2-) in vitro or in vivo. FCLA(3,7-dihydro-6-{4-[2-(N'-(5-fluoresceinyl)thioureido)ethoxy]phenyl}-2-methylimidazo{1,2-a}pyrazin-3-one sodium salt), a chemiluminescence (CL) analysis reagent, has been reported to sensitively react with 1O2 and O2- to emit photons with a spectral peak of 525nm. In this work, when human serum albumin (HSA) was added into FCLA solution to enhance the CL intensity, approximately 20 times, compared to that without HSA. The enhanced CL had the same 525 nm spectral peak, identical to that without HSA. By gradually reducing the molecular oxygen content in the solution, we find that the auto-oxidation of oxygen molecules dissolved in the solution plays an important role in the CL process. Based on these experimental evidences, we propose a novel and highly sensitive detection method of 1O2 and O2-, which may have a great potential in chemical and medical applications.

An efficient strategy for photocatalytic hydrogen peroxide production over oxygen-enriched graphitic carbon nitride with sodium phosphate

Photocatalytic hydrogen peroxide(H_(2)O_(2))production is a promising strategy to replace the traditional production processes;however,the inefficient H_(2)O_(2) productivity limits its application.In this study,oxygen-rich g-C_(3)N_(4) with abundant nitrogen vacancies(OCN)was synthesized for photocatalytic H_(2)O_(2) production.X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy indicated that oxygen-containing functional groups(–COOH and C–O–C)were obtained.Electron paramagnetic resonance confirmed the successful introduction of nitrogen vacancies.OCN exhibited efficient photocatalytic H_(2)O_(2) production performance of 1965μmol L^(−1) h^(−1) in air under visible-light irradiation.The high H_(2)O_(2) production was attributed to the enhanced adsorption of oxygen,enlarged specific surface area,and promoted carrier separation.An increased H_(2)O_(2) production rate(5781μmol L^(−1) h^(−1))was achieved in a Na_(3)PO_(4) solution.The improved performance was attributed to the changed reactive oxygen species.Specifically,the adsorbed PO_(4)^(3−) on the surface of the OCN promoted the transfer of holes to the catalyst surface.•O_(2)−obtained by O_(2) reduction reacted with adjacent holes to generate 1O_(2),which could efficiently generate H_(2)O_(2) with isopropanol.Additionally,PO_(4)^(3−),as a stabilizer,inhibited the decomposition of H_(2)O_(2).

NEW EREMOPHILANOLIDES FROM LIGULARIA VEITCHIANA

The structures of three new eremophilanolides isolated from the roots of Ligularia Veitchiana were shown,by the spectral and chemical evidences,to be 1β,10β-epoxy-6β- hydrox-y-8β-methoxy-eremophil-7(11)-en-12,8α-olide(3),1β,10β-epoxy-6β- (2'-hydroxymethylacryloyloxy)-8β-methoxy-eremophil-7(11)-en-12,8α-olide (4)and 1β,10β-epoxy-6β-(2'-methoxymethylacryloyloxy)-8β-hydroxy-eremophil -7(11)-en-12,8α-olide(5).

SINGLET OXYGEN DETECTION DURING PHOTOSENSITIZATION

Singlet oxygen(^(1)O_(2))is a highly reactive oxygen species involved in numerous chemical and photochemical reactions in diferent biological systems and in particular,in photodynamic therapy(PDT).However,the quantifcation of^(1)O_(2) generation during in vitro and in vivo pho-tosensitization is still technically challenging.To address this problem,indirect and direct methods for^(1)O_(2)detection have been intensively studied.This review presents the available methods currently in use or under development for detecting and quantifying^(1)O_(2) generation during photosensitization.The advantages and limitations of each method will be presented.Moreover,the future trends in developing PDT-^(1)O_(2) dosimetry will be briefly discussed.

Meso-substituted cationic 3-and 4-N-Pyridylporphyrins and their Zn(II)derivatives for antibacterial photodynamic therapy

Photodynamic inactivation of microorganisms known as antibacterial photodynamic therapy(APDT)is one of the most promising and innovative approaches for the destruction of pathogenic microorganisms.Among the photosensitizers(PSs),compounds based on cationic porphyrins/metalloporphyrins are most successfully used to inactivate microorganisms.Series of meso-substituted cationic pyridylporphyrins and metalloporphyrins with various peripheral groups in the third and fourth positions of the pyrrole ring have been synthesized in Armenia.The aim of this work was to determine and test the most e®ective cationic porphyrins and metalloporphyrins with high photoactivity against Gram negative and Gram positive microorganisms.It was shown that the synthesized cationic pyridylporphyrins/metalloporphyrins exhibit a high degree of phototoxicity towards both types of bacteria,including the methicillinresistant S.aureus strain.Zinc complexes of porphyrins are more phototoxic than metal-free porphyrin analogs.The e®ectiveness of these Zn–metalloporphyrins on bacteria is consistent with the level of singlet oxygen generation.It was found that the high antibacterial activity of the studied cationic porphyrins/metalloporphyrins depends on four factors:the presence in the porphyrin macrocycle of a positive charge(+4),a central metal atom(Zn2þÞand hydrophobic peripheral functional groups as well as high values of quantum yields of singlet oxygen.The results indicate that meso-substituted cationic pyridylporphyrins/metalloporphyrins cannd wider application in photoinactivation of bacteria than anionic or neutral PSs usually used in APDT.

Theoretical Study on the Structure and Isomerization of CH_3SB

The structure and mechanism of isomerization of CH3SB have been studied by using DFT method at the B3LYP/6-311G** level. The computational results reveal that the energy of singlet state of CH3SB is lower than that of triplet state, so the former should be the ground state. Two transition states of isomerization of singlet state of CH3SB have been determined at the B3L-YP/6- 311G** level, too. The methyl linked to sulfur atom is first transferring to the boron atom, to which the hydrogen atom of methyl is then transferring. According to the results of this paper, reaction paths of isomerizations of CH3SB are studied thoroughly with IRC method.

Projectile and target excitation in He^(+)+He collisions at intermediate energies

We present ab initio calculations of cross sections for projectile and target excitation occurring in the course of He^(+)+He collisions using a threeactive-electron semiclassical nonperturbative approach.Intermediate impact energies ranging from 1 keV to 225 keV/u are considered.The results of our calculations agree well with available measurements for both projectile and target excitation in the respective overlapping energy regions.A comparison of our results with those of other theoretical calculations further demonstrates the importance of a nonperturbative approach that includes a sufficient number of channels.Furthermore,it is found that the cross sections for target excitation into singlet states show a valley centered at about 25 keV/u,resulting from competition with electron transfer to singlet projectile states.By contrast,the cross sections for target excitation into triplet states do not exhibit any such structures.

Correlation of in vivo tumor response and singlet oxygen luminescence detection in mTHPC-mediated photodynamic therapy

Excited-state singlet axygen(^(1)O_(2)),generated during photodynamic therapy(PDT),is believed to be the primary cytotoxic agent with a number of clinically approved photosensitizers.Its relative concentration in cells or tissues can be measured directly through its near-infrared(NIR)luminescence emission,which has correlated well with in vitro cell and in triro normal skin treatment responses.Here,its correlation with the response of tumor tiss1e in vito is examined,using the photosensitizer meso-tetralydroxyphenylchlorin(mTHPC)in an animal model comprising luciferase-and green fluorescent protein(GFP)-transduced gliosarcoma grown in a dorsal window chamber.The change in the bioluminescence signal,imaged pre-treatment and at 2,5 and 9 d post treatment,was used as a quantitative measure of the tumor response,which was classified in individual tumors as"non","moderate"and"strong"in order to reduce the variance in the data.Plotting the bioluminescence-based response vs the^(1)O_(2)counts demonstrated clear correlation,indicating tha^(1)O_(2)luminescence provides a valid do-simetric technique for PDT in tumor tissue.