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On the determination of quantum yields for singlet molecular oxygen photosensitization
... PDT involves the use of a photoactive drug (photosensitiser) and light (typically visible or infrared) [1,2]. Upon absorption of light, the photosensitiser (PS) initiates chemical reactions that lead to the direct or indirect production of cytotoxic species such as radicals and singlet oxygen [3,4]. The reaction of the cytotoxic species with subcellular organelles and macromolecules (proteins, DNA, etc) lead to apoptosis and/or necrosis of the cells hosting the PS. ...
... In PDT, absorption of light by the PS initiates chemical reactions that produce transient phototoxic compounds. The mechanism of production of these transient species has been thoroughly described elsewhere [1,4,14,15]. Briefly photodynamic mechanisms proceed from the first excited single state (S 1 ) of the photosensitiser produced by the absorption of a photon elsewhere [14]. ...
Photodynamic therapy (PDT) is an anticancer combination therapy, which requires a photosensitiser, which tends to accumulate preferentially in the tumour, and light. Historically large, complex lasers have been used to carry out PDT treatment. Nowadays there is a wide range of coherent and non-coherent sources that can be used. This paper considers the important characteristics of light sources for PDT, including dye lasers pumped by argon or metal vapour lasers and frequency-doubled Nd:YAG lasers. Non-laser sources including tungsten filament, xenon arc, metal halide and fluorescent lamps are also discussed. New exciting developments such as LEDs and femtosecond lasers are also reviewed. The relative merits of laser and non-laser sources are critically examined.
... Experiments were conducted in phosphate D 2 O buffer to increase the lifetime of the generated singlet oxygen and to enhance the detection sensitivity. 50 The quantum yield of singlet oxygen photogeneration for both aminofullerenes was obtained using TMAP as a standard and it was determined to be around 0.1 and 0.062 (HexakisaminoC 60 vs MonoaminoC 60 , Figures S12 and S18); in the case of MMS48, the tetraphenylporphirine (TPP) was used as a standard, in a chloroform solution ( Figure S20). Although it is not a high yield for HexakisaminoC 60 , in the presence of serum albumin the formation of singlet oxygen was markedly increased ( Figure 3B), what was also measured quantitively ( Figure S22). ...
Skin cancer is the most common cancer in the USA and Europe. Its subtype, squamous skin carcinoma (SCC), if allowed to grow, has the potential to metastasize and can become deadly. Currently, carbon nanomaterials are being developed to treat cancer due to their attractive physicochemical and biological properties such as an enhanced permeability effect and their ability to produce reactive oxygen species. Here, we describe the synthesis of two water-soluble aminofullerenes (MonoaminoC60 and HexaaminoC60), which were evaluated as novel [60]fullerene based photosentizers exhibiting anti-cancer properties. Moreover, the previously described neutral glycofullerene GF1 and its peracetylated lipophilic precursor MMS48 were compared with the aminofullerenes for their ability to generate reactive oxygen species and oxidize lipids. Remarkably, the generation of singlet oxygen and a superoxide radical by HexaaminoC60 was found to be markedly elevated in the presence of bovine serum albumin and NADH, respectively. Mechanistic studies of lipid peroxidation using cholesterol as a unique reporter molecule revealed that although all four fullerene nanomaterials primarily generated singlet oxygen, superoxide anion was also formed, which suggest a mixed mechanism of action (in which Type I and Type II photochemistry is involved). The [60]fullerene derivative HexaaminoC60 was also studied for its phototoxicity in squamous skin cancer cell line (A431) using the MTT test and propidium iodide staining.
Photodynamic therapy (PDT) involves the use of a photoactive drug (photosensitizer) and light. Upon absorption of light, the photosensitizer initiates oxygen-mediated chemical reactions that lead to the direct or indirect production of species such as singlet oxygen that cause cell death. The reaction of the cytotoxic species with subcellular organelles and molecules such as proteins and DNA lead to apoptosis or necrosis of the cells hosting the photosensitizer. Preferential accumulation of photosensitizer in cancer cells means that, as an anti-cancer treatment, this has the potential to kill selectively the tumor cells while leaving healthy cells undamaged. Photodynamic mechanisms proceed from the first excited singlet state (S1) via either Type I or Type II mechanism. A Type I reaction involves the photosensitizer losing an electron to form a radical cation, typically reacting with oxygen to form superoxide and hydroxyl radicals. In a Type II reaction, the sensitizer relaxes into the first excited triplet state (T1) which interacts with oxygen to form singlet oxygen. The species produced are very reactive and can cause cell death by either apoptosis or necrosis. Cells membranes are a primary site of action. Functional impairment of mitochondria is also observed.
A sensitive method for the quantitative determination of singlet oxygen based on a low-cost laser deflection calorimeter (LDC) apparatus is presented. The heat released from the singlet oxygen generation and its nonradiative decay in an aqueous phase causes the formation of a thermally driven refractive index gradient in an adjacent organic phase. This effect, which is proportional to the amount of singlet oxygen generated, is monitored by the deflection of a laser beam. Limits of detection (LOD) obtained were in the sub-μmol level which is one order of magnitude lower than the LOD obtained by measuring the “dimol” emission at 633 run. This method should be specially designed for studying chemical and biochemical processes at interfaces by measuring low amounts of heat released.
Understanding the interactions of non-ionizing radiation with living organisms has been the focus of much research over recent decades. The complex nature of these interactions warrants development of theoretical and experimental studies to gain an insight into predicting and monitoring the success of photodynamic therapy (PDT) protocols. There is a major impetus towards evidence-based recommendations for patient diagnosis, treatment and management. Knowledge of the biophysical aspects of PDT is important for improving dosimetry protocols. Fluorescence in clinical PDT may be used to detect and diagnose pre-malignant and malignant conditions, while photobleaching can monitor changes in fluorescence during treatment. Combining empirical fluorescence photobleaching clinical data with computational modelling enables clinical PDT dosimetry protocols to be investigated with a view to optimising treatment regimes. We will discuss how Monte Carlo radiation transfer (MCRT) modelling has been intercalated in the field of fluorescence detection and PDT. In this paper we highlight important aspects of basic research in PDT by reporting on the current utilisation of fluorescence in clinical PDT from both a clinical and theoretical perspective. Understanding and knowledge of light propagation in biological tissue from these perspectives should have a positive impact on treatment planning.
Photodegradation processes of carbocyanine dyes spin-coated on a polycarbonate plate were studied by steady-state photolysis and near-IR emission spectroscopy. The efficiency of the whole photodegradation caused by molecular oxygen directly and/or indirectly was found to strongly depend on both substituents on the 1 and 1‘ positions and the counterion. Singlet molecular oxygen (1Δg) produced at the interface between the dye thin film and a polycarbonate plate was detected by near-IR emission spectroscopy. Its yield did not depend on substituents on the 1 and 1‘ positions but on the counterion. The relative reactivity of carbocyanine dyes in the film state with the singlet molecular oxygen was estimated by exploiting a perinaphthenone thin film as a singlet molecular oxygen generator. The reactivity strongly depended on both substituents on the 1 and 1‘ positions and the counterion.
The interaction of 4,5',8-trimethylpsoralen (TMP) with molecular oxygen in a variety of solvents has been investigated using pulsed, time-resolved photoacoustic calorimetry and fluorescence emission. In this work we propose a methodology for the absolute determination of the quantum yield for the photosensitized production of singlet molecular oxygen, based on data from time resolved photoacoustics. The methodology also allows the determination of the quenching rate constant of the sensitizer triplet state by oxygen as well as the intersystem crossing quantum yield, provided the energy level of the triplet state is known. The methodology has been checked with two well-known photosensitizing agents, rose bengal and methylene blue. We found that in all of the solvents investigated, the production of singlet oxygen by TMP is a process with relatively high probability and may therefore play an important role in the overall reactivity of the molecule. For comparison, photoacoustic data for 8-methoxypsoralen (8-MOP) are reported, showing that singlet oxygen photosensitization is low in all of the solvents examined.
We present protoporphyrin IX (PpIX) fluorescence measurements acquired from patients presenting with superficial basal cell carcinoma during photodynamic therapy (PDT) treatment, facilitating in vivo photobleaching to be monitored. Monte Carlo (MC) simulations, taking into account photobleaching, are performed on a three-dimensional cube grid, which represents the treatment geometry. Consequently, it is possible to determine the spatial and temporal changes to the origin of collected fluorescence and generated singlet oxygen. From our clinical results, an in vivo photobleaching dose constant, β of 5-aminolaevulinic acid-induced PpIX fluorescence is found to be 14 ± 1 J/cm(2). Results from our MC simulations suggest that an increase from our typical administered treatment light dose of 75-150 J/cm(2) could increase the effective PDT treatment initially achieved at a depth of 2.7-3.3 mm in the tumor, respectively. Moreover, this increase reduces the surface PpIX fluorescence from 0.00012 to 0.000003 of the maximum value recorded before treatment. The recommendation of administrating a larger light dose, which advocates an increase in the treatment time after surface PpIX fluorescence has diminished, remains valid for different sets of optical properties and therefore should have a beneficial outcome on the total treatment effect.
Since ancient times, many cultures worldwide found out independently that the topical administration of some photoactive natural products (mainly extracted from plants) followed by exposure to sunlight, might be an effective treatment of some skin diseases, thus accidently giving birth to the so-called photochemotherapy. In the attempt to resemble nature by exploiting its teaching, during the last two centuries, scientists tried to rationalize this knowledge in order to develop more effective therapeutic strategies and to understand in depth the mechanisms of action involved, expanding the potential application of this therapy to pathologies other than skin diseases, such as some types of tumors. In this paper we aim at giving an overview on results achieved to date on state-of-the-art photochemotherapy related to the treatment of cancer. The script is organized in three sections. Subsequent to a general introduction describing the origin and basic principles of photochemotherapy, the first section deals with the issue concerning the choice of the proper light sources for each type of therapeutic application, stressing the technological advances in the field (e.g. fiber optics). The second and the third sections provide an overview of the two clinically-established phototherapies to date, that is, PUVA photochemotherapy and PDT, respectively. Both sections are further subdivided into sub-paragraphs emphasizing specific relate topics such as principles and applications, employed light sources, and available data concerning anticancer activity. The third section also provides examples of non-conventional metal-based photosensitizers for PDT.
Quenching of excited singlet and triplet states of many substances by ground state molecular oxygen produces singlet oxygen, the lowest electronically excited singlet state of molecular oxygen, O[sub 2]([sup 1][Delta][sub g]). The fractions of singlet and triplet states quenching which produce singlet oxygen and the quantum yields of formation of singlet oxygen in fluid solutions have been critically compiled. Methods for determining yield parameters have been reviewed. Data have been compiled from the literature through 1991. Photosensitizers such as aromatic hydrocarbons, aromatic ketones and thiones, quinones, coumarins, fluoresceins, transition metal complexes, and heterocyclics are included in Table 1. Porphyrins and phthalocyanines are included in Table 2. Other materials which have been investigated for singlet oxygen production, such as dyes and drugs, are collected in Table 3 along with heterogeneous systems such as polymer-bound photosensitizers. 79 refs., 4 figs., 3 tabs.
