Photodynamic therapy (PDT) as a cancer treatment for global health: Insights from development of low-cost technology for image-guided PDT of early oral cancer in India

The World Health Organization reports that more than 60% of new cancer cases and 70% of deaths annually occur in low and middle income countries (LMICs). A lack of medical infrastructure for timely diagnosis and treatment of cancer in LMICs drives this disparity and motivates the development of low-cost technologies that are specifically adapted for use in resource-limited settings. We have developed technology to enable use of photodynamic therapy (PDT) with aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) for treatment of early-stage oral malignancy in India, which has been described as the “oral cancer capital of the world.” As a light-based approach PDT is inherently conducive to LMIC adaptation using LEDs as a low-cost source for visible wavelengths that can readily provide irradiance in the range of 10’s of mW/cm² for small lesions. Our team developed a portable, battery-powered, fiber-coupled 635nm LED light source with a system of interchangeable 3D printed applicators for ergonomic light delivery to lesions of varying size and position in the oral cavity. The system uses an embedded microcontroller and Bluetooth to interface with a smartphone while an attachment for imaging PpIX fluorescence is used for treatment guidance and monitoring. Clinical evaluation in partnership with collaborators in India has shown excellent outcomes, with complete tumor response in 73% of oral cancer patients following a single PDT treatment. Here we discuss ongoing technology development to continue to optimize intraoral PDT light delivery and improve image guidance during treatment, as well as challenges and opportunities moving forward for broader implementation and adaptation to other indications.     

Enhancing the efficiency of 5-aminolevulinic acid-mediated photodynamic therapy using 5-fluorouracil on human melanoma cells

Background5-Aminolevulinic acid-mediated photodynamic therapy (ALA–PDT) is an effective and noninvasive modality for treatment of several types of non-melanoma skin cancers. This in-vitro study attempted to know whether the killing effect of ALA–PDT on the human melanoma cells (Mel-Rm cell line) could be increased by the presence of 5-fluorouracil (5-FU).MethodsTo evaluate the effect of ALA–PDT in combination with 5-FU on viability of human melanoma Mel-Rm cells, the cells incubated with 5-ALA and 5-FU for 3 h in nontoxic concentrations, and subsequently illuminated with a 630 nm light-emitting diode array. The cells viability and cytotoxicity determined by mitochondrial activity and lactate dehydrogenase assays.ResultsCombination of ALA–PDT and 5-FU (FU–ALA–PDT) showed a considerable growth inhibition according to the results of MTT assay compared to ALA–PDT. The results of LDH assay also showed a cytotoxicity effect in ALA–PDT; however, the FU–ALA–PDT showed no significantly enhancement in cytotoxicity compared to ALA–PDT using LDH assay.ConclusionThe Mel-Rm cells incubation with 5-FU before PDT enhances the efficiency of 5-Aminolevulinic acid-mediated photodynamic therapy.     

Radiosensitization/radioprotection: Methods of Analysis

Summary

The transformation and mutagenic potential of porphyrin photodynamic therapy has been examined in mammalian cells. The mutagenic frequency in Chinese hamster cells at the Na⁺/K⁺ ATPase locus was measured by resistance to ouabain following treatment with either photodynamic therapy (PDT) or UV irradiation. The C3H 10T 1/2 mouse embryo cell system was used to document the transformation frequency following PDT, UV irradiation, gamma irradiation or exposure to 3-methylocholanthrene (MCA). Treatments with UV irradiation were effective in producing mutants resistant to ouabain, and treatments with UV irradiation, gamma irradiation and MCA generated transformants at frequencies comparable to those which are reported in the literature. However, PDT treatment conditions (which produced a full range of cytotoxicity) did not induce any mutagenic or transformation activity above background levels.     

5-aminolevulinic acid and sodium ferrous citrate decreased cell viability of gastric cancer cells by enhanced ROS generation through improving COX activity

BackgroundMitochondrial dysfunctions are related to cancer development.. 5-aminolevulinic acid (ALA) is used for photodynamic therapy (PDT). In this PDT, protoporphyrin IX (PpIX), which is converted from ALA, can generate reactive oxygen species (ROS) that kill the cancer cell. ALA is also reported to promote cytochrome c oxidase (COX) activity, which can generate ROS itself. Therefore, this study focused on the effect of ALA during PDT. In addition, in the previous study, sodium ferrous citrate (SFC) is reported to increase COX activity. So, this study also aims to improve the COX activity by the addition of SFC that can promote ROS generation, which has a cytotoxic effect.MethodsIn this study, we used ALA and SFC, then evaluated the effects of the treatment on the human gastric cancer cell line MKN45, including the induction of cell death.ResultsThis study showed that treatment with ALA and SFC increases intracellular heme and heme proteins. Moreover, COX activity was promoted, resulting in the production of intracellular reactive oxygen species (ROS), which eventually reduced the cell viability in human gastric cancer cell line MKN45.ConclusionOur study can detect ROS generation with ALA and SFC. Furthermore, we found this generation of ROS has a cytotoxic effect. Therefore, this phenomenon contributes to the effect of PDT.     

Periodic Mesoporous Ionosilica Nanoparticles: Versatile Nano-objects for Imaging,Photodynamic Therapy,Drug Delivery and siRNA Gene Silencing

We report the use of Periodic Mesoporous Ionosilica Nanoparticles (PMINPs) as versatile nano-objects for imaging, photodynamic therapy (PDT), drug delivery and efficient adsorption and delivery of siRNA into breast cancer cells. The synthesized mesoporous ionosilica nanoparticles are well known for several advantages: high specific area and uniformity of both size and shape of pores^[1]. In order to confer to these nanoparticles PDT and siRNA photochemical internalization (PCI) properties, a porphyrin derivative was integrated into the ionosilica framework.Our results indicate the formation of highly porous nanorods. A significant PDT effect was observed for both one-photon^[2] and two-photon excitation PDT, due to an important ROS production upon light irradiation in nanoparticles treated-breast cancer cells. Zeta potential measurements of PMINPs revealed the presence of positive surface charges which promoted the adsorption of siRNA and BODIPY molecules. The electrostatic complexation of siRNA was then verified by electrophoresis gel retardation assay. Furthermore, PMINPs formed stable complexes with siRNA (up to 24 hours) and were efficiently internalized into the cells after 4 hours incubation mostly with energy-dependent endocytosis process. The PCI effect was obvious under light irradiation and successfully led to luciferase gene silencing in luciferase-expressing breast cancer cells, while no gene silencing effect was observed in the absence of light. The dual effect of gene silencing by siRNA and PDT was also studied and revealed the existence of a synergistic effect.This work highlights the potential of porphyrin-doped ionosilica nanoparticles as multifunctional drug nanocarriers for nucleic acids, such as siRNA, with a triple ability to perform imaging, PDT and PCI.     

Current status of PDT in the United States

The field of photodynamic therapy (PDT) continues to make significant progress in the United States of America (USA). There are currently about 23 recruiting interventional clinical studies designed to evaluate the safety and efficacy of PDT in adult patients, in the USA [1]. Skin cancer and lung cancer are the primary sites with four studies investigating PDT for the treatment of basal cell carcinoma (BCC), one study using PDT to treat non-melanoma skin cancer in patients with solid organs transplant, three evaluating PDT in the treatment of actinic keratosis, and another study aims to treat acne. Three studies evaluating PDT in the treatment of non-small cell lung cancer with pleural disease, two of these studies include malignant mesothelioma, and one targeting locally advanced and metastasis that induce airway obstruction. In other disease sites there is one study that evaluates PDT in the treatment of head and neck cancer, non-muscle invasive bladder cancer, pancreatic cancer, esophageal cancer, anal cancer, prostate cancer or low-grade upper tract urothelial cancer. One study evaluates PDT in the treatment neurofibromatosis type 1, and one study evaluates the safety and feasibility of PDT to sterilize deep tissue abscess cavities.Several photosensitizers are being used with investigational new drug approval or exemption by the USA food and drug administration (FDA) [1]. The FDA-approved porfimer sodium is being used to treat locally advanced lung cancer or lung cancer with pleural disease, malignant central airway obstruction, malignant mesothelioma, and head and neck cancer. The topical pro-drug, aminolevulinic acid (ALA) is being used to treat BCC and anal cancer, while one study adds 4% imipramine cream to ALA PDT to treat microvesicle particle in the skin. A vascular drug, padeliporfin dipotassium, is being evaluated in the treatment of early-stage prostate cancer and low-grade upper tract urothelial cancer. A ruthenium polypyridyl complex administered by instillation is being evaluated for efficacy in treating non-muscle invasive bladder cancer. Verteporfin is being evaluated for efficacy in the treatment of pancreatic cancer. The safety and feasibility of PDT with methylene blue is being evaluated for sterilizing deeply seated abscess cavities.Treatment planning and dosimetry are being employed by measuring light dose rate (irradiance) and dose (fluence), as well as singlet oxygen. There is no system that is currently approved for clinical use in the USA. The National Institutes of Health supports about 40 investigators-initiated projects in the USA [2]. Most of these projects focus on developing novel methods to improve the response to PDT. These include advanced treatment planning and dosimetry systems, imaging using photoacoustic or theranostic approaches, combination therapies that utilize PDT to enhance the response to chemotherapy, use of Vitamin D to improve treatment outcomes and employing molecular targeted probes and functional nanoparticles and liposomes.Acknowledgement: Thanks to Dr. Sherri McFarland for her constructive suggestions and comments.Conflict of interest: Dr. Shafirstein is a co-inventor of the optical surface applicator and dosimetry system (USPTO 11,344,742, 11,040,217). He acknowledges current service on a scientific advisory board with honoraria and stock options from Lumeda Inc.; receiving grant support from Lumeda Inc.; receiving in-kind contributions from Pinnacle Biologics Inc., and grant support from Johnson and Johnson Enterprise Innovation, Inc.     

Fluorescence evaluations for porphyrin formation during topical PDT using ALA and methyl-ALA mixtures in pig skin models

BackgroundPhotodynamic Therapy (PDT) using Aminolevulinic acid (ALA) and derivative molecules as topical medication and as a precursor of protoporphyrin (PPIX), is limited due to low permeation through skin or efficiency in porphyrin production. This behavior affects the production and homogeneity of PPIX distribution on superficial skin and in the deeper skin layers. Many authors propose alternatives to solve this such as, modification in the ALA and derivativemolecules, modifying the chemical properties of emulsion external phase or incorporating a delivery system to the emulsion. The goal of this study is to discuss what proportion of ALA and Methyl aminolevulinate (MAL) on mixtures increase the amount and uniformity of PPIX formation at superficial skin by fluorescence evaluations.MethodsThe study was conducted in vivo using a pig skin model. PPIX production was monitored using fluorescence spectroscopy and widefield fluorescence imaging on skin surface. 20% of ALA and MAL cream were done mixing the following proportions: ALA, M2 (80% ALA–20% MAL), M3 (60% ALA–40% MAL), M4 (50% ALA–MAL), M5 (40% ALA–60% MAL), M6 (20% ALA–80% MAL) and MAL.ResultsMixtures M3, M4, and M5 showed the most PPIX production on skin by widefield fluorescence imaging and fluorescence spectroscopy in 3 h of incubation. These results suggest that 50% of ALA and MAL in the same mixture increase the PPIX production in amount, homogeneity and time production when compared to ALA and MAL. This has a positive impact on photodynamic damage optimizing the PDT treatment.     

Theranostic Silver Chalcogenide Quantum Dots in Phototherapy

Nanoparticles entered the phototherapy arena as photosensitizers and as delivery vehicles of organic photosensitizers. Luminescent Ag-chalcogenide quantum dots trigger PTT at long wavelengths and offer image-guided phototherapy. These nanoparticles also effectively deliver organic photosensitizers such as 5-aminolevulinic acid (ALA) and/or drugs to the target, hence provide PDT/PTT, Chemo/PTT, or even Chemo/PDT/PTT combination for effective killing of tumor cells.Nanoparticles entered the phototherapy arena as photosensitizers and as delivery vehicles of organic photosensitizers. 4-Aminolevulinic acid is now an FDA-approved pro-drug for PDT suffering from low bioavailability. Small theranostic nanoparticles that are already under heavy investigation for drug delivery and tracking offer the opportunity to improve ALA-bioavailability and delivery to targets, such as the tumor mass.Ag₂S quantum dots are luminescent in the NIR and highly biocompatible, hence are excellent for delivering ALA and providing image-guided PDT. We have loaded Ag₂S with ALA and tagged it with Cetuximab for improved and selective PDT of EGFR(+) colorectal cancer cells under 420 nm and 630 nm irradiation [1]. This enabled improved PDT with a significantly low ALA dose: 0.17 mM ALA-1 min – 640 nm irradiation caused more than 80% death in SW480 cell line after a short incubation. Further toxicity was obtained with additional 5FU conjugation to these QDs and almost all cells were killed at and above 0.35 mM ALA/15 μg mL⁻¹ 5FU doses, which is dramatically lower than IC50 of each component. Ag₂S QDs were also discovered as photosensitizers for PTT [3,4] and a combination of image-guided PTT and chemotherapy potential was investigated in cancer cells, using folic acid tagged Ag₂S QDs loaded with methotrexate [2]. This approach provided selective and near complete killing of FR(+) HeLa cells compared to HT29 and A549 cells via necrosis/late apoptosis after 10 min irradiation at 808 nm. IC₅₀ of MTX was reduced from 10 to 0.21 μg/mL.Lastly, in vivo examples of chemo/PTT combinations for the treatment of breast cancer will be shown.     

In vitro assessment of anti-tumorigenic mechanisms and efficacy of NanoALA,a nanoformulation of aminolevulic acid designed for photodynamic therapy of cancer

BackgroundThe development of nanocarriers is an important approach to increase the bioavailability of hydrophilic drugs in target cells. In this work, we evaluated the anti-tumorigenic mechanisms and efficacy of NanoALA, a novel nanoformulation of aminolevulic acid (ALA) based on poly(lactide-co-glycolide) (PLGA) nanocapsules designed for anticancer photodynamic therapy (PDT).MethodsFor this purpose, physicochemical characterization, prodrug incorporation kinetics, biocompatibility and photocytotoxicity tests, analysis of the cell death type and mitochondrial function, measurement of the intracellular reactive oxygen species production and DNA fragmentation were performed in murine mammary carcinoma (4T1) cells.ResultsNanoALA formulation, stable over a period of 90 days following synthesis, presented hydrodynamic diameter of 220 ± 8.7 nm, zeta potential of −30.6 mV and low value of polydispersity index (0.28). The biological assays indicated that the nanostructured product promotes greater ALA uptake by 4T1 cells and consequently more cytotoxicity in the PDT process. For the first time in the scientific literature, there is a therapeutic efficacy report of approximately 80%, after only 1 h of incubation with 100 μg mL⁻¹ prodrug (0.6 mM ALA equivalent). The mitochondria are probably the initial target of treatment, culminating in energy metabolism disorders and cell death by apoptosis.ConclusionsNanoALA emerges as a promising strategy for anticancer PDT. Besides being effective against a highly aggressive tumor cell line, the treatment may be economically advantageous because it allows a reduction in the dose and frequency of application compared to free ALA.     

5-氨基酮戊酸-光动力学疗法作用于白血病细胞的研究--细胞实验中PDT剂量计算的数学模型

目的 将5-氨基酮戊酸-光动力学疗法(ALA-PDT)应用于血液肿瘤的研究开创了AIA-PDT研究的一个新领域，本文对该领域的作用机理的数学模型及细胞实验进行了研究。方法 主要建立细胞实验中PDT剂量计算的数学模型。结果 数学模型中所推导的一些参数都是实验或临床中可观测和调制的量，其基本参量包括：光功率密度E、ALA的细胞孵育量P和光照持续时间T等。结论 论文主要的试验数据获得包括：PDT剂量(ALA剂量及孵育时间，光波长及剂量范围)的摸索；ALA-PDT后血细胞活性的检测；影响ALA-PDT疗效的因素等。论文对ALA-PDT的剂量计算进行了建模分析，通过上述式子就可计算出PDT中涉及的很多参量。     

In-Vitro Use of Verteporfin for Photodynamic Therapy in Glioblastoma

BackgroundStummer et al. established fluorescence-guided surgery (FGS) for glioblastoma (GBM) using 5-aminolevulinic acid (5-ALA). Its metabolite, protoporphyrin IX (PPIX), is also a photosensitizer and can be used for photodynamic therapy (PDT) using a laser beam of 635 nm. The porphyrin derivate verteporfin (VP) was discovered to have properties to penetrate the brain, pharmacologically target glioma cells, and is approved for PDT of choroidal neovascularization in wet age-related macular degeneration at 689 nm.ObjectiveTo elucidate whether GBM cell lines are susceptible to PDT with second-generation photosensitizer VP.MethodsHuman glioma cell lines LN229, HSR-GBM1, and a low-passage patient-derived GBM cell line P1 were treated with variable concentrations of VP for 24 h, followed by PDT at 689 nm using a diode laser light. Cell viability was measured using the MTT assay and VP uptake was measured using a desktop cytometer.ResultsSignificantly higher cell death following PDT with VP compared to VP treatment alone or no treatment was detected in all cell models (LN229, HSR-GBM1, P1). Flowcytometric measurements revealed a concentration-dependent cellular uptake of VP after 24 h incubation up to 99% at 10 µM (HSR-GBM1).ConclusionThis study demonstrates that PDT with VP causes cell death in GBM cells at marginal concentrations. Additionally, red spectrum fluorescence was detected at therapeutic concentrations in all cell lines, validating the cellular uptake of VP in GBM cells. VP, therefore, is not only a potential drug for targeting GBM pharmacologically but can be used as an optical imaging dye in surgery and photosensitizer to make GBM susceptible to PDT.     

The influence of storage conditions on delta amino levulinic acid induced toxicity and phototoxicity in vitro

Delta amino levulinic acid photodynamic therapy (ALA-PDT) represents one of the most prominent advances in PDT. ALA itself or its derivatives are marketed for a variety of clinical indications. Despite the development of clinical applications, experimental ALA results are very heterogeneous and experimentally used parameters are still not standardized. This suggests that some problems remain unsolved that are likely to impair experiments to be performed but also that clinical results obtained could be greatly improved. Frequently unmentioned or imprecise data concern solvents, pH of ALA solutions, storage time, ALA degradation or ALA efficacy. In addition, diversity of experimental model is huge while capabilities of ALA transformation into PpIX are known to vary from one cell to the other. Thus, the aim of the present paper was to quantify the level of ALA degradation or changes in ALA efficacy using one single cell line without presuming of the mechanisms and determine the conditions of storage inducing the best transformation into PpIX and/or cell phototoxicity. We added ALA diluted in water, PBS or RPMI to C6 cells, a murine brain tumour cell line that can be used in vivo as an orthotopic graft. We measured in cells used as tools for final bio efficacy estimation, both the induced fluorescence and phototoxicity in various conditions of storage before use chosen to be as close as possible to the real lab conditions. Water had been found to better preserve ALA than, respectively, PBS and RPMI and this for any temperature or storage durations. The lowest temperature and the shortest duration for storage used had also been shown to better preserve ALA-induced fluorescence and phototoxicity. The fact that these properties were found to be better preserved in 7.4 buffered solvent could be in relationship with a fast ALA condensation occurring at neutral or lightly acidic pH modifying its availability for an optimal transformation into PpIX.     

In vivo and in vitro models for photodynamic therapy by using novel photosensitizers

Photodynamic therapy (PDT) is an effective treatment for both malignant and non-malignant diseases, and new photosensitizers / chromophores are studied by confocal imaging and biological techniques determining cell survival with/without light. During PDT the activated PS transfers energy to nearby oxygen molecules, generating singlet oxygen (¹O₂) resulting in oxidative stress (ROS), which further elicit cell death by necrosis and apoptosis. Protoporphyrin IX (PpIX), is an efficient and widely used PS for bladder superficial bladder cancer treatment; either endogenously produced in the cancer cells by e. g. aminolaevulinic acid (ALA) or exogenously added as e. g. hexyl-ALA. The effects in vitro and in vivo are present by using an orthotopic rat cancer model; also included pphotochemical internalization (PCI). This is a new strategy for local enhancement of various types of drug molecules by employing a photosensitising compound and illumination of a diseased area in the body. The possibility of using PCI to enhance effects of the cytotoxic drug bleomycin is investigated, together with photophysical determinations and outlines of a treatment for intravesical therapy of bladder cancer. In vitro experiments indicate that employment of PCI technology using the novel photosensitizer TPCS_2a® enhance cytotoxic effects of bleomycin in bladder cancer cells. Furthermore, experiments in an orthotopic in vivo bladder cancer model show effective reduction in both necrotic area and bladder weight after TPCS_2a based photodynamic therapy (PDT). The tumor selectivity and PDT effects may be sufficient to destroy tumors without damaging detrusor muscle layers. Our results present a possible new treatment strategy for non-muscle invasive bladder cancer, with intravesical instillation of photosensitizer and bleomycin followed by illumination through an optic fiber by using a catheter.     

Synthesis,characterisation and in vitro investigation of photodynamic activity of 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride on HeLa cells using low light fluence rate

Photodynamic therapy (PDT) is a treatment that aims to kill cancer cells by reactive oxygen species, mainly singlet oxygen, produced through light activation of a photosensitiser (PS). Amongst photosensitisers that attracted the most attention in the last decade are cationic and amphiphilic molecules based on porphyrin, chlorin and phthalocyanine structures. Our aim was to join this search for more optimal balance of the lipophilic and hydrophilic moieties in a PS. A new amphiphilic porphyrin, 5-(4-octadecanamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride (5) was synthesised and characterised by ¹H NMR, UV–vis and fluorescence spectroscopy, and by MALDI-TOF/TOF spectrometry. In vitro photodynamic activity of 5 was evaluated on HeLa cell lines and compared to the activity of the hydrophilic 5-(4-acetamidophenyl)-10,15,20-tris(N-methylpyridinium-3-yl)porphyrin trichloride (7). Low fluence rate (2 mW cm⁻²) of red light (643 nm) was used for the activation, and both porphyrins showed a drug dose-response as well as a light dose-response relationship, but the amphiphilic porphyrin was presented with significantly lower IC₅₀ values. The obtained IC₅₀ values for 5 were 1.4 μM at 15 min irradiation time and 0.7 μM when the time of irradiation was 30 min, while for 7 these values were 37 and 6 times higher, respectively. These results confirm the importance of the lipophilic component in a PS and show a potential for 5 to be used as a PS in PDT applications.     

Bare fiber photodynamic therapy using porfimer sodium for esophageal disease

During Digestive Disease Week 2005 in Chicago, Illinois, our group of 10 gastrointestinal photodynamic therapists met to discuss variations in procedural technique and treatment protocols. An extensive review of the use of photodynamic therapy (PDT) for esophageal disease has recently been published elsewhere [Wolfsen HC. Present status of photodynamic therapy for high-grade dysplasia in Barrett's esophagus. J Clin Gastroenterol 2005;39(3):189–202]. This report, based mostly on clinical experience and common sense rather than evidence-based medicine, is a detailed discussion of pragmatic issues. In summary, our centers treat patients with Barrett's dysplasia, Barrett's or squamous cell carcinoma using the photosensitizer porfimer sodium (2 mg/kg total body weight) and bare fiber PDT (no fiber centering devices). Aggressive suppression of gastric acid is uniformly emphasized. The most common technique variables were the light energy source, light dosimetry and the amount of Barrett's mucosa treated during a course of PDT. Standardization of porfimer sodium PDT procedures and light dosimetry may enhance treatment outcomes.     

光动力治癌新药血卟啉单甲醚（HMME）的研究

本文报道了一种单体卟啉血卟啉单甲醚的合成及其光敏化力、人癌细胞光灭活作用、动物移植瘤光动力疗效和有关的临床前药理毒理学研究资料。实验结果表明,与临床应用的混合卟啉制剂血卟啉衍生物(HpD)相比,HMME具有光敏化力强、肿瘤选择性摄入率高、光动力效应强、毒性低、无致突变和致畸胎作用等优点,是一种较理想的光动力治癌新药。     

光敏剂PSD-007对人骨肉瘤MG-63细胞体外光动力作用的实验观察

目的观察PSD-007对人骨肉瘤MG-63细胞的光动力效应。方法以人骨肉瘤MG-63细胞为研究对象,测定以PSD-007作为光敏剂,630 nm波长激光为光源,不同能量密度激光的PDT处理后MG-63细胞的OD492值,并绘制MG-63细胞PDT后的存活率曲线,光镜下观察PDT后MG-63细胞形态的变化。结果 PSD-007浓度为2μg/ml,激光能量密度为6 J/cm2时,PDT处理后MG-63细胞存活率明显降低,仅为48.09%。PDT后MG-63细胞形态发生明显的变化,部分细胞坏死。结论 PSD-007对人骨肉瘤MG-63细胞具有明显的抑制作用。     

Photodynamic therapy in the treatment of rosacea: A systematic review

ObjectiveTo systematically review the efficacy of photodynamic therapy (PDT) in the treatment of rosacea.MethodsPubMed, Embase, and Cochrane Library databases were searched for articles published by February 5, 2022, using “photodynamic therapy” and “rosacea” as the keywords.ResultsNine studies were included in the review. The number of patients varied from 1 to 30 in each study, with ages ranging from 18 to 76 years. Methyl aminolevulinate (MAL) and aminolevulinic acid (ALA) were used as the photosensitizer, and red light, blue light, intense pulsed light (IPL), long-pulsed dye laser (LPDL), pulsed dye laser (PDL), and tungsten lamp were used as the light or laser source. The follow-up time ranged from one month to 25 months. Most of the studies showed a satisfactory clinical response, and the side effects were tolerant and temporary.ConclusionCurrent studies have provided preliminary evidence that PDT is an efficient and safe therapy in treating rosacea. However, rigorous randomized control trials (RCTs) with a larger sample size and longer follow-up time are warranted to verify the curative effects of PDT in treating rosacea and explore the most appropriate treatment schedule.     

DNA damages after SIM01 photodynamic treatment

Photodynamic therapy (PDT) is a new approach to cancer treatment for a variety of malignant tumors. A new photosensitizer, 2,3-dihydro-5,15-di(3,5-dihydroxyphenyl)porphyrin (SIM01), had been evaluated for its genotoxic effects on glioma cells (C6). Comet assay had been used to evaluate the potential genotoxic effect induced by SIM01 on the C6 cells. When SIM01 had been shown to be a powerful sensitizer no DNA strand break was detected in the absence of light. SIM01 localized in cytoplasm but not in the nucleus of the tumors cells, which supported the finding of undetectable DNA damage under darkness and low photodynamic dose.Cell exposure to 20 J cm⁻² after an incubation time of 2 h with 0, 0.25, 0.5, 2 or 4 μg mL⁻¹ induced less than 25% of cell death but significant Tail Moment changes. If DNA damage intensity increased according to SIM01 doses under light exposure, importance of repair seemed to increase proportionally to PDT-induced damage. Positive controls consisted of doxorubicin-treated C6 cells this mutagen being known to induce genetic damage. Whatever the conditions used SIM01 appeared to be less deleterious than doxorubicin. As the comet assay can not give us the certitude that no mutation, photoadducts or oxidative damage had been developed under light exposure this point will have to be verified with another mutagenicity assay. SIM01 appears to be safe from a mutagenic point of view something of importance as tumors of small volume in patients with a long lifespan are at first indicated for PDT.