Energy Transfer between AGuIX Nanoparticles and Photofrin under Light or X-ray Excitation for PDT Applications.

Photodynamic therapy is an accepted therapy cancer treatment. Its advantages encourage researchers to delve deeper. The use of nanoparticles in PDT has several advantages including the passive targeting of cancer cells. The aim of this article is to evaluate the effectiveness of AGuIX nanoparticles (activation and guiding of irradiation by X-ray) in the presence or absence of a photosensitizer, Photofrin, under illumination of 630 nm or under X-ray irradiation. The goal is to improve local tumor control by combining PDT with low-dose-X-ray-activated NPs in the treatment of locally advanced metastatic lung cancer. The study of the energy transfer, which occurs after excitation of Gd/Tb chelated in AGuIX in the presence of Photofrin, was carried out. We could observe the formation of singlet oxygen after the light or X-ray excitation of Gd and Tb that was not observed for AGuIX or Photofrin alone, proving that it is possible to realize energy transfer between both compounds.

Clinical PDT dose dosimetry for pleural Photofrin-mediated photodynamic therapy.

Significance: Photodynamic therapy (PDT) is an established cancer treatment utilizing light-activated photosensitizers (PS). Effective treatment hinges on the PDT dose-dependent on PS concentration and light fluence-delivered over time. We introduce an innovative eight-channel PDT dose dosimetry system capable of concurrently measuring light fluence and PS concentration during treatment. Aim: We aim to develop and evaluate an eight-channel PDT dose dosimetry system for simultaneous measurement of light fluence and PS concentration. By addressing uncertainties due to tissue variations, the system enhances accurate PDT dosimetry for improved treatment outcomes. Approach: The study positions eight isotropic detectors strategically within the pleural cavity before PDT. These detectors are linked to bifurcated fibers, distributing signals to both a photodiode and a spectrometer. Calibration techniques are applied to counter tissue-related variations and improve measurement accuracy. The fluorescence signal is normalized using the measured light fluence, compensating for variations in tissue properties. Measurements were taken in 78 sites in the pleural cavities of 20 patients. Results: Observations reveal minimal Photofrin concentration variation during PDT at each site, juxtaposed with significant intra- and inter-patient heterogeneities. Across 78 treated sites in 20 patients, the average Photofrin concentration for all 78 sites is 4.98 µM, with a median concentration of 4.47 µM. The average PDT dose for all 78 sites is 493.17 µMJ/cm2, with a median dose of 442.79 µMJ/cm2. A significant variation in PDT doses is observed, with a maximum difference of 3.1 times among all sites within one patient and a maximum difference of 9.8 times across all patients. Conclusions: The introduced eight-channel PDT dose dosimetry system serves as a valuable real-time monitoring tool for light fluence and PS concentration during PDT. Its ability to mitigate uncertainties arising from tissue properties enhances dosimetry accuracy, thus optimizing treatment outcomes and bolstering the effectiveness of PDT in cancer therapy.

Fractionated Photofrin-Mediated Photodynamic Therapy Significantly Improves Long-Term Survival.

This study investigates the effect of fractionated (two-part) PDT on the long-term local control rate (LCR) using the concentration of reactive oxygen species ([ROS]rx) as a dosimetry quantity. Groups with different fractionation schemes are examined, including a 2 h interval between light delivery sessions to cumulative fluences of 135, 180, and 225 J/cm2. While the total treatment time remains constant within each group, the division of treatment time between the first and second fractionations are explored to assess the impact on long-term survival at 90 days. In all preclinical studies, Photofrin is intravenously administered to mice at a concentration of 5 mg/kg, with an incubation period between 18 and 24 h before the first light delivery session. Fluence rate is fixed at 75 mW/cm2. Treatment ensues via a collimated laser beam, 1 cm in diameter, emitting light at 630 nm. Dosimetric quantities are assessed for all groups along with long-term (90 days) treatment outcomes. This study demonstrated a significant improvement in long-term survival after fractionated treatment schemes compared to single-fraction treatment, with the optimal 90-day survival increasing to 63%, 86%, and 100% vs. 20%, 25%, and 50%, respectively, for the three cumulative fluences. The threshold [ROS]rx for the optimal scheme of fractionated Photofrin-mediated PDT, set at 0.78 mM, is significantly lower than that for the single-fraction PDT, at 1.08 mM.

Evaluation of Fractionated Photofrin-mediated Photodynamic Therapy Using Different Light Fluences with Reactive Oxygen Species Explicit Dosimetry (ROSED).

Photodynamic therapy (PDT) is an established modality for cancer treatment, and reactive oxygen species explicit dosimetry (ROSED), based on direct measurements of in-vivo light fluence (rate), in-vivo photofrin concentration, and tissue oxygenation concentration, has been proved to provide the best dosimetric quantity which can be used to predict non-fractionated PDT outcome. This study performed ROSED for Photofrin-mediated PDT for mice bearing radiation-induced fibrosacorma (RIF) tumor. As demonstrated by our previous study, fractionated PDT with a 2-hour time interval can significantly improve the long-term cure rate (from 15% to 65% at 90 days), and it tends to increase as the light dose for the first light fraction gets larger. This study focused on further improving the long-term cure rate without introducing apparent toxicity using combinations of different first light fraction lengths and total light fluences. Photofrin was injected through the mouse tail vein at a concentration of 5 mg/kg. After 18~24 hours, treatment was delivered with a collimated laser beam of 1 cm diameter at 630 nm. Mice were treated using two fractions of light fluences with a 2-hour dark interval. Different dose metrics were quantified, including light fluence, PDT dose, and [ROS]rx. In addition, the total reacted [ROS]rx and treatment outcomes were evaluated and compared to identify the optimal light fraction length and total light fluence.

Multispectral singlet oxygen luminescent dosimetry (MSOLD) for Photofrin-mediated Photodynamic Therapy.

Direct detection of singlet-state oxygen ([1O2]) constitutes the holy grail dosimetric method for type II PDT, a goal that can be quantified using multispectral singlet oxygen dosimetry (MSOLD). However, the short lifetime and extremely weak nature of the singlet oxygen signal produced has given rise to a need to improve MSOLD signal-to-noise ratio. This study examines methods for optimizing MSOLD signal acquisition, specifically employing an orthogonal arrangement between detection and PDT treatment light, consisting of two fiber optics - connected to a 632-nm laser and an InGaAs detector respectively. Light collected by the InGaAs detector is then passed through a filter wheel, where spectral emission measurements are taken at 1200 nm, 1240 nm, 1250 nm, 1270 nm, and 1300 nm. The data, after fitting to the fluorescence background and a gaussian-fit for the singlet oxygen peak, is established for the background-subtracted singlet oxygen emission signal. The MSOLD signal is then compared with the singlet oxygen explicit dosimetry (SOED) results, based on direct measurements of in-vivo light fluence (rate), in-vivo Photofrin concentration, and tissue oxygenation concentration. This study focuses on validating the sensitivity and minimum detectability of MSOLD signal in various in-vitro conditions. Finally, the MSOLD device will be tested in Photofrin-mediated PDT for mice bearing Radiation-Induced Fibrosarcoma (RIF) tumors.

Lipophilicity prediction of three photosensitizers by liquid-liquid extraction, HPLC, and DFT methods.

Photodynamic therapy (PDT) is a method of treating precancerous diseases and malignant neoplasms. The efficacy of PDT depends on different parameters such as light dosimetry, oxygen availability, and photophysical and physical-chemical properties of the photosensitizer. In PDT, a photosensitizer is activated using light to promote oxygen photosensitization and cellular transport plays a key role in the reach of it to the desired tissue. In particular, to know the effectiveness of the drug delivery in PDT and its dosage forms to target damaged organs, along with such characteristics as water solubility, it is important to know the ability of a substance to penetrate through cell membrane or accumulate in it. Lipophilicity is used to quantify the earlier-described abilities. We evaluated the lipophilicity of three selected photosensitizers (PS) (protoporphyrin IX, pyropheophorbide-a and photofrin) by means of three different methods: octanol-water distribution methods (shake-flask), reversed-phase high-performance liquid chromatography (HPLC) and theoretical calculations based on density functional theory (DFT). We describe and compare the results of these various methods.

Photodynamic therapy to a primary cancer of the peripheral lung: Case report.

Photodynamic therapy (PDT) is an FDA approved treatment for lung cancer. In the United States the photosensitizer porfimer sodium (Photofrin®, Pinnacle Biologics) is intravenously introduced at 2mg/kg. After approximately 48 h, illumination to activate the photosensitizer is initiated, with 630nm red light at 200J/cm, delivered by fiber-optic catheter, brought to the tumor endo- bronchially, and delivered for 500 s. This will create, in the presence of oxygen, a Type II Photodynamic Reaction (PDR) which generates singlet oxygen species that are tumor ablative. Classically, PDT for lung cancer has been employed for symptomatic central and obstructing tumors with great success. This case report describes an innovative approach to treat a peripheral, early stage lung cancer employing magnetic navigation and endobronchial treatment. We report on a 79 year old male with numerous comorbidities including pulmonary fibrosis, who was found to have a biopsy proven peripheral and solitary non-small cell cancer. Due to prior SBRT (stereotactic body radiation therapy) with dose levels causing radiation fibrosis, he was not a candidate for repeat SBRT, and he was not a surgical candidate due to comorbidities. Tumor control with PDT was achieved without treatment related morbidity. This report details our findings.

Reactive oxygen species explicit dosimetry (ROSED) for fractionated photofrin-mediated photodynamic therapy (PDT).

Photodynamic therapy (PDT) is an established modality for cancer treatment and reactive oxygen species explicit dosimetry (ROSED), based on direct measurements of in-vivo light fluence (rate), in-vivo photofrin concentration, and tissue oxygenation concentration, has been proved to be an effective dosimetric quantity which can be used to predict PDT outcome. In this study, ROSED was performed for photofrin-mediated PDT for mice bearing radiation-induced fibrosacorma (RIF) tumor. PDT treatments were performed using single or fractionated illumination to a same total fluence of 135 Jcm-2. The effects of light fractionation on the total reacted [ROS]rx and treatment outcomes were evaluated.

Validation of multispectral singlet oxygen luminescence dosimetry (MSOLD) for photofrin-mediated photodynamic therapy.

Accurate dosimetry is crucial for the ongoing development and clinical study of photodynamic therapy (PDT). Current dosimetry standards range from less accurate methods involving measurement of only light fluence and photosensitizer concentration during treatment, to significantly improved methods such as singlet oxygen explicit dosimetry (SOED), a macroscopic model that includes an additional important parameter in its dosimetric calculations: ground-state oxygen concentration ([3O2]). However, neither of these models is a method of direct dosimetry. Multispectral singlet oxygen luminescence dosimetry (MSOLD) shows promise in this regard but requires significant improvement in signal quality and remains to be validated in a clinical setting. In this study, we validate a linearly increasing MSOLD signal with an InGaAs photodiode detector for increasing concentration (0 mg/kg to 200 mg/kg) in tissue-simulating phantoms containing photofrin, calculating a calibration curve based on 1270 nm peak-intensity signal and area under the curve for background-subtracted singlet oxygen emission. Additionally, we validate MSOLD against the current clinical dosimetry standard, SOED, through simultaneous measurement of SOED parameters and MSOLD signal for varying concentrations (50 µM - 300 µM). Finally, we investigate the effects of using very high gain amplification on InGaAs photodiode detectors to amplify the MSOLD signal for use in clinical models. We show that a calibration curve relating photosensitizer concentration (PS) and MSOLD signal can be established. Additionally, we demonstrate good correlation between MSOLD signal and SOED-calculated [1O2]rx. However, we show that when using high amplification on InGaAs photodiodes for long illumination times, the inherent instability in these detectors becomes apparent.

Real-time PDT Dose Dosimetry for Pleural Photodynamic Therapy.

PDT dose is the product of the photosensitizer concentration and the light fluence in the target tissue. For improved dosimetry during plural photodynamic therapy (PDT), an eight-channel PDT dose dosimeter was developed to measure both the light fluence and the photosensitizer concentration simultaneously from eight different sites in the pleural cavity during PDT. An isotropic detector with bifurcated fibers was used for each channel to ensure detected light was split equally to the photodiode and spectrometer. The light fluence rate distribution is monitored using an IR navigation system. The navigation system allows 2D light fluence mapping throughout the whole pleural cavity rather than just the selected points. The fluorescence signal is normalized by the light fluence measured at treatment wavelength. We have shown that the absolute photosensitizer concentration can be obtained by applying optical properties correction and linear spectral fitting to the measured fluorescence data. The detection limit and the optical property correction factor of each channel were determined and validated using tissue-simulating phantoms with known varying concentration of Photofrin. Tissue optical properties are determined using an absorption spectroscopy probe immediately before PDT at the same sites. The combination of 8-channel PDT dosimeter system and IR navigation system, which can calculate light fluence rate in the pleural cavity in real-time, providing a mean to determine the distribution of PDT dose on the entire pleural cavity to investigate the heterogeneity of PDT dose on the pleural cavity.

Photodynamic Therapy for Colorectal Cancer: A Systematic Review of Clinical Research.

BACKGROUND: Photodynamic therapy (PDT) is a therapeutic modality that can be used to ablate tumors using the localized generation of reactive oxygen species by combining a photosensitizer, light, and molecular oxygen. This modality holds promise as an adjunctive therapy in the management of colorectal cancer and could be incorporated into neoadjuvant treatment plans under the auspices of prospective clinical trials. METHODS: We conducted a search of primary literature published until January 2021, based on PRISMA guidelines. Primary clinical studies of PDT for the management of colorectal cancer were included. Screening, inclusion, quality assessment, and data collection were performed in duplicate. Analyses were descriptive or thematic. RESULTS: Nineteen studies were included, most of which were case series. The total number of patients reported to have received PDT for colorectal cancer was 137, almost all of whom received PDT with palliative intent. The most common photosensitizer was hematoporphyin derivative or Photofrin. The light dose used varied from 32 J/cm2 to 500 J/cm2. Complete tumor response (cure) was reported in 40%, with partial response reported in 43.2%. Symptomatic improvement was reported in 51.9% of patients. In total, 32 complications were reported, the most common of which was a skin photosensitivity reaction. CONCLUSIONS: PDT for the management of colorectal cancer has not been well studied, despite promising results in early clinical case series. New, well designed, prospective clinical trials are required to establish and define the role of PDT in the management of colorectal cancer.

Photodynamic therapy for peripheral lung cancer.

Photodynamic therapy (PDT) is an internationally approved ablation technique for endo-bronchial lung cancer. The majority of reported outcomes are for central and obstructing lesions where excellent long term control is possible. With the current trend of screening high risk for lung cancer populations, a larger cohort of patients are now diagnosed with earlier stage disease. When these early tumors are located in the lung periphery the current therapeutic options include surgery or radiation therapy. Still, many patients may not be candidates or amenable for these procedures. As PDT is a well tolerated non-thermal outpatient therapy to treat lung cancer and as newer bronchoscopy techniques allow for treatment of peripheral lesions, PDT may be an option. We report a case of a primary non-small cell lung cancer treated by interstitial PDT through placement of the diffusing fiber via magnetic navigational bronchoscopy. Forty eight hours post 2 mg/kg intravenous (IV) injection of Photofrin®, a single 500 second illumination of 200 J/cm at 630 nm was directed to the solitary peripheral lesion without complication. On day 30, as a part of planned therapy, lobectomy was undertaken. Pathology reported necrosis and no viable remaining tumor. At 90 days follow up, the patient remains well,with no evidence of disease. Additional details follow in the report.

Microfluidic system with light intensity filters facilitating the application of photodynamic therapy for high-throughput drug screening.

BACKGROUND: Photodynamic therapy utilizes light energy with a photosensitizer (a light-sensitive drug) to kill cancer cells through creation of singlet oxygen via light activation. When a photosensitizer is injected into the bloodstream and exposed to a specific wavelength of light, it generates oxygen to destroy or damage nearby cancer cells, while minimizing side effects on normal cells. Although photodynamic therapy is effective for treating cancer, various parameters, such as the optimum light intensity and photosensitizer dose, are currently poorly understood due to the complexity of conventional experimental schemes. METHODS: To effectively perform a simultaneous single parallel test for several different light irradiation conditions on each cell, a microfluidic device was developed to generate eight different intensities from a single light-emitting diode source, through eight different color dye concentrations functioning as light intensity filters. To show that this novel high-throughput microfluidic system can analyze the effects of various light intensities during photodynamic therapy, the optimum light intensities and photosensitizer doses were determined for two different cancer cell lines. RESULTS: Optimum light intensities and photosensitizer were determined for all cell lines. The photodynamic therapy effects in response to different irradiated light intensities were characterized by analyzing cell viability after photosensitizer treatment CONCLUSIONS: : The developed platform is capable of being used as a photodynamic therapy screening tool. The proposed platform provides a simple and robust way to optimize the combined parameters of light intensity and dosage for diverse types of cancer cells.

Disinfection of radicular dentin using Riboflavin, Rose Bengal, Curcumin, and Porfimer sodium on extrusion bond strength of fiber post to radicular dentin.

AIM: To assess the influence of different photosensitizers activated by PDT as a disinfectant in comparison to conventional sodium hypochlorite (NaOCl) on the EBS (extrusion bond strength) of FRCP with radicular dentin. METHODS: A total of fifty single-rooted human maxillary central incisors with fully developed apices were selected. Endodontic treatment of samples was performed using 10 K file to obtain patency than sequentially with a 25 K file followed by rotary pro tapers till F2 with constant irrigation. The canal was dried and obturated with corresponding gutta-percha and sealer. A Peso reamer was employed to prepare post space. Based on canal disinfection regimes, samples were divided into five groups. Group 1 Riboflavin (RF)+17%EDTA, group 2 Rose bengal (RB) +17%EDTA, group 3 Curcumin CP +17%EDTA, group 4 Porfimer sodium, Photofrin (PS) +17%EDTA and group 5 2.25% NaOCl +17% EDTA (control). Following disinfection, the canal space of all specimens was dried followed by FRCP cementation. Specimens were placed on a Universal testing machine (UTM) for EBS. The type of bond failure was evaluated using a stereomicroscope. ANOVA and Tukey multiple comparison tests were used to compare means. RESULTS: The highest EBS was shown by group 1 canal disinfected with riboflavin (RF) and 17% EDTA at all three levels. The lowest EBS was displayed in group 5 canal cleaned with 2.25% NaOCl and 17% EDTA. Intragroup assessment disclosed a decrease in EBS from cervical one-third to apical one-third in all experimental groups. Intergroup comparison revealed group 4 using PS and 17% EDTA and group 5 canal disinfected with 2.25% NaOCl and 17% EDTA at all three levels of root structure coronal, middle, and apical exhibited comparable EBS (p>0.05). CONCLUSION: Root canal dentin treated with different PS (RF, RB, CP) has the potential to be used as canal disinfection as it demonstrates better EBS than the conventional disinfecting regime (2.25% NaOCl +17% EDTA). PS and 17% EDTA as a canal disinfectant need further investigation.

Estimation of fluorescence probing depth dependence on the distance between source and detector using Monte Carlo modeling.

Photosensitizer fluorescence emission during photodynamic therapy (PDT) can be used to estimate for in vivo photosensitizer concentration. We built a surface contact probe with 405nm excitation light source to obtain Photofrin fluorescence signal during clinical PDT. The probe was equipped with multiple detector fibers that were located at distances between 0.14 to 0.87 cm laterally from the excitation source fiber. In this study, we investigated the probing depth of fluorescence in biological tissue with different source-detector separation using our contact probe setup. We used Monte Carlo method to simulate the 405nm excitation light and 630nm fluorescence probing depth at various source and detector (SD) separations. The results provided insight to the most probable depth of origin of detected fluorescence at each SD separation and help to understand the in vivo depth distribution of clinically measured Photofrin concentration.

Photophysical Properties of Protoporphyrin IX, Pyropheophorbide-a and Photofrin® in Different Conditions.

Photodynamic therapy (PDT) is an innovative treatment of malignant or diseased tissues. The effectiveness of PDT depends on light dosimetry, oxygen availability, and properties of the photosensitizer (PS). Depending on the medium, photophysical properties of the PS can change leading to increase or decrease in fluorescence emission and formation of reactive oxygen species (ROS) especially singlet oxygen (1O2). In this study, the influence of solvent polarity, viscosity, concentration, temperature, and pH medium on the photophysical properties of protoporphyrin IX, pyropheophorbide-a, and Photofrin® were investigated by UV-visible absorption, fluorescence emission, singlet oxygen emission, and time-resolved fluorescence spectroscopies.

Porphyrin-lipid nanovesicles (Porphysomes) are effective photosensitizers for photodynamic therapy.

Porphysomes (PS) are liposome-like nanoparticles comprising pyropheophorbide-conjugated phospholipids that have demonstrated potential as multimodal theranostic agents for applications that include phototherapies, targeted drug delivery and in vivo fluorescence, photoacoustic, magnetic resonance or positron emission imaging. Previous therapeutic applications focused primarily on photothermal therapy (PTT) and suggested that PSs require target-triggered activation for use as photodynamic therapy (PDT) sensitizers. Here, athymic nude mice bearing subcutaneous A549 human lung tumors were randomized into treatment and control groups: PS-PDT at various doses, PS-only and no treatment negative controls, as well as positive controls using the clinical photosensitizer Photofrin. Animals were followed for 30 days post-treatment. PS-PDT at all doses demonstrated a significant tumor ablative effect, with the greatest effect seen with 10 mg/kg PS at a drug-light interval of 24 h. By comparison, negative controls (PS-only, Photofrin-only, and no treatment) showed uncontrolled tumor growth. PDT with Photofrin at 5 mg/kg and PS at 10 mg/kg demonstrated similar tumor growth suppression and complete tumor response rates (15 vs. 25%, p = 0.52). Hence, porphysome nanoparticles are an effective PDT agent and have the additional advantages of multimodal diagnostic and therapeutic applications arising from their intrinsic structure. Porphysomes may also be the first single all-organic agent capable of concurrent PDT and PTT.

Synergistic effect of glycated chitosan and photofrin photodynamic therapy on different breast tumor model.

Metastases and recurrence of cancer are the main causes of failure and death. Induction of a long-term tumor specific immunity seems to be a great strategy to deal with this challenge. Laser immunotherapy (LIT), using immunomodulatory techniques in combination with photodynamic therapy (PDT), so as to enhance an already robust immune response, has been proposed and investigated by numerous researchers. In our study, mice bearing EMT6 breast tumors and 4T1 metastatic breast tumors were addressed in various permutations of the different components in LIT. The survival rates and the tumor growth curve of EMT6 breast tumors bearing mice were analyzed. We compared the level of inflammatory reaction, cell apoptosis and activated immune cells infiltration of local tumors. We validated the systemic effect of LIT through the 4T1 metastatic breast tumors bearing mice. The results not only proved that concomitant with Glycated chitosan (GC) can improve the effect of inhibiting the tumor growth, improving survival, enhancing local inflammatory reaction and attracting acted immune cells to tumor by photodynamic therapy with Photofrin, but also intuitively proved the systemic effect and long-term effect of LIT.

Blood Flow Measurements Enable Optimization of Light Delivery for Personalized Photodynamic Therapy.

Fluence rate is an effector of photodynamic therapy (PDT) outcome. Lower light fluence rates can conserve tumor perfusion during some illumination protocols for PDT, but then treatment times are proportionally longer to deliver equivalent fluence. Likewise, higher fluence rates can shorten treatment time but may compromise treatment efficacy by inducing blood flow stasis during illumination. We developed blood-flow-informed PDT (BFI-PDT) to balance these effects. BFI-PDT uses real-time noninvasive monitoring of tumor blood flow to inform selection of irradiance, i.e., incident fluence rate, on the treated surface. BFI-PDT thus aims to conserve tumor perfusion during PDT while minimizing treatment time. Pre-clinical studies in murine tumors of radiation-induced fibrosarcoma (RIF) and a mesothelioma cell line (AB12) show that BFI-PDT preserves tumor blood flow during illumination better than standard PDT with continuous light delivery at high irradiance. Compared to standard high irradiance PDT, BFI-PDT maintains better tumor oxygenation during illumination and increases direct tumor cell kill in a manner consistent with known oxygen dependencies in PDT-mediated cytotoxicity. BFI-PDT promotes vascular shutdown after PDT, thereby depriving remaining tumor cells of oxygen and nutrients. Collectively, these benefits of BFI-PDT produce a significantly better therapeutic outcome than standard high irradiance PDT. Moreover, BFI-PDT requires ~40% less time on average to achieve outcomes that are modestly better than those with standard low irradiance treatment. This contribution introduces BFI-PDT as a platform for personalized light delivery in PDT, documents the design of a clinically-relevant instrument, and establishes the benefits of BFI-PDT with respect to treatment outcome and duration.

The feasibility of using Saffron to reduce the photosensitivity reaction of selected photosensitizers using red blood cells and staphylococcusAureus bacteria as targets.

BACKGROUND: The photosensitivity reaction which appears after a Photodynamic therapy treatment session is a challenge that needs further investigation. The goal of this research is to evaluate the possibility of using saffron to reduce or control this photosensitivity reaction and to present mathematical modeling of the cell survival curves and their dependency on saffron concentration. METHODS: Red blood cells (RBC) and Staphylococcus aureus Bacteria (STB) were used as targets in this study. The Photosensitivity of Rose Bengali, Methylene Blue, and Photofrin independently and incorporated with saffron was investigated for continued irradiation at different Saffron concentrations. Gompertz's function was used to fit the survival curve parameters. The 50% cell survival rate was fit to an empirical formula based on Saffron concentrations. RESULTS: Saffron inhibits the photosensitivity reaction of the three photosensitizers and causes a significant increase in the 50% survival rate time (t50) for RBC`s and STB. Saffron didn't show phototoxicity when incubated alone with RBC`s and STB. The survival curve parameters of the RBCs and STB showed a good fit to the Gompertz function. Saffron concentration is related to the RBC`s t50 based on power dependency of 0.56, 0.38 and 0.31 for Photofrin, Methylene Blue and Rose Bengali respectively and 0.1 on STB for Rose Bengali. CONCLUSION: Saffron can efficiently be used to reduce the photosensitivity reaction of Photosensitizers after a PDT treatment session. Gompertz function was found to be an appropriate mathematical model for survival rate curves. The t50 and the saffron concentration are well related through a power dependence empirical formula.