Photodynamic Therapy Of Skin Cancer Research Articles

Tea polyphenols nanoparticles integrated with microneedles multifunctionally boost 5-aminolevulinic acid photodynamic therapy for skin cancer

5-aminolevulinic acid photodynamic therapy (ALA-PDT) is an emerging therapeutic strategy for skin cancer due to its noninvasiveness and high spatiotemporal selectivity. However, poor skin penetration, poor intratumoral delivery, the instability of aqueous ALA, and the tumor’s inherent hypoxia microenvironment are major hurdles hindering the efficacy of ALA-PDT. Herein, we aim to address these challenges by using microneedles (MNs) to assist in delivering nanoparticles based on natural polymeric tea polyphenols (TP NPs) to self-assemble and load ALA (ALA@TP NPs). The TP NPs specifically increase cellular uptake of ALA by A375 and A431 cells and reduce mitochondrial membrane potential. Subsequently, the photosensitizer protoporphyrin IX derived from ALA accumulates in the tumor cells in a dose-dependent manner with TP NPs, generating reactive oxygen species to promote apoptosis and necrosis of A375 and A431 cells. Interestingly, TP NPs can ameliorate the tumor’s inherent hypoxia microenvironment and rapid oxygen consumption during PDT by inhibiting hypoxia inducible factor-1α, thereby boosting reactive oxygen species (ROS) generation and enhancing ALA-PDT efficacy through a positive feedback loop. After ALA@TP NPs are loaded into MNs to fabricate ALA@TP NPs@MNs, the MNs enhance skin penetration and storage stability of ALA. Importantly, they exhibit remarkable antitumor efficacy in A375-induced melanoma and A431-induced squamous cell carcinoma with a reduced dose of ALA and reverse hypoxia in vivo. This study provides a facile and novel strategy that integrates MNs and green NPs of TP for addressing the bottlenecks of ALA-PDT and enhancing the ALA-PDT efficacy against skin cancers for future clinical translation.

Optical design of a tunable microneedle array for photodynamic therapy of metastatic melanomas

The need for photodynamic therapy is increasing with the rise of skin cancer melanoma detection. However, low penetration depth of light in the UV range and higher scattering of skin tissues cause harsh clinical practices and reduced irradiance for the activation of chemicals such as photosensitizers to facilitate cell necrosis of malignant tumors. In this paper, a tunable microlens integrated on a microneedle array is designed for variable focusing to reduce melanomas at multiple sites with an improved intensity for reactive oxygen species production. A light distribution of 36% percent of the input intensity is achieved at the targeted distance of 4.35 mm for blue light. Red light attained a light distribution of 13% of the input intensity at a targeted distance of 6.5 mm. Designing such a light, delivery-based in-vivo biomedical device is of extreme importance for photodynamic therapy of skin cancer on and beyond the epidermal tissue layer.

Dissolving Microneedle-Based Cascade-Activation Nanoplatform for Enhanced Photodynamic Therapy of Skin Cancer.

Photodynamic therapy (PDT) has been an attractive strategy for skin tumor treatment. However, the hypoxic microenvironment of solid tumors and further O2 consumption during PDT would diminish its therapeutic effect. Herein, we developed a strategy using the combination of PDT and hypoxia-activated bioreductive drug tirapazamine (TPZ). TPZ was linked to DSPE-PEG-NHS forming DSPE-PEG-TPZ to solve leakage of water-soluble TPZ and serve as an antitumor agent and monomer molecule further forming the micellar. Chlorin e6 (Ce6) was loaded in DSPE-PEG-TPZ forming DSPE-PEG-TPZ@Ce6 (DPTC). To further improve tumor infiltration and accumulation, hyaluronic acid was adopted to make DPTC-containing microneedles (DPTC-MNs). Both in vitro and in vivo studies consistently demonstrated the synergistic antitumor effect of photodynamic therapy and TPZ achieved by DPTC-MNs. With laser irradiation, overexpressions of PDT tolerance factors NQO1 and HIF-1α were inhibited by this PDT process. The synergistic effect of PDT and TPZ significantly improved the performance of DPTC-MNs in the treatment of melanoma and cutaneous squamous cell carcinoma and has good biocompatibility.

Microemulsions Improve Topical Protoporphyrin IX (PpIX) Delivery for Photodynamic Therapy of Skin Cancer

Microemulsions Improve Topical Protoporphyrin IX (PpIX) Delivery for Photodynamic Therapy of Skin Cancer

Chitosan-functionalized nanostructured lipid carriers containing chloroaluminum phthalocyanine for photodynamic therapy of skin cancer

The objective of this study was to obtain optimized nanostructured lipid carriers (NLC) functionalized with chitosan containing chloroaluminum phthalocyanine (ClAlPc) as a photosensitizer. Initially, the optimization of the preparation method of the NLC was performed, where the influence of different surfactants such as PVA and Tween 80, as well as different solid lipids such as stearic acid and Glycerol Monostearate (GM) was evaluated. The formulation containing GM and PVA (NLC10) was considered promising. Following, by the adsorption method (NLC10q), the formulation was functionalized with chitosan and characterized. NLC10 and NLC10q presented sizes of 131.5 and 231.5 nm, and ZP of −24.30 and + 19.96 mV, respectively. The encapsulation efficiency of NLC10q was 96 %, higher than NLC10 (79 %). The formulations were able to promote significant cutaneous retention of ClAlPc, after 2 h and 4 h of the study, and showed to be non-toxic to fibroblasts (biocompatible). PDT in BF16-F10 melanoma resulted in reduced cell viability to 70 % and 50 % for NLC10 and NLCq, respectively. In view of the results obtained, NLC showed to be promising in the treatment of skin cancer through PDT. NLC10q showed higher encapsulation efficiency and stability than NLC10, but, contrary to what was expected, it presented lower photodynamic efficiency.

Oxidative Stress and Photodynamic Therapy of Skin Cancers: Mechanisms, Challenges and Promising Developments.

Ultraviolet radiation is one of the most pervasive environmental interactions with humans. Chronic ultraviolet irradiation increases the danger of skin carcinogenesis. Probably, oxidative stress is the most important mechanism by which ultraviolet radiation implements its damaging effects on normal cells. However, notwithstanding the data referring to the negative effects exerted by light radiation and oxidative stress on carcinogenesis, both factors are used in the treatment of skin cancer. Photodynamic therapy (PDT) consists of the administration of a photosensitiser, which undergoes excitation after suitable irradiation emitted from a light source and generates reactive oxygen species. Oxidative stress causes a condition in which cellular components, including DNA, proteins, and lipids, are oxidised and injured. Antitumor effects result from the combination of direct tumour cell photodamage, the destruction of tumour vasculature and the activation of an immune response. In this review, we report the data present in literature dealing with the main signalling molecular pathways modified by oxidative stress after photodynamic therapy to target skin cancer cells. Moreover, we describe the progress made in the design of anti-skin cancer photosensitisers, and the new possibilities of increasing the efficacy of PDT via the use of molecules capable of developing a synergistic antineoplastic action.

Development of a system to treat and online monitor photodynamic therapy of skin cancer using PpIX near-infrared fluorescence.

The limited adoption of photodynamic therapy (PDT) around the medical field may be tied to the unpredicted treatment response that an unmonitored therapy could deliver. Given the high variability in the lesions optical and physiological parameters, it is of fundamental importance to monitor PDT, since different lesions require different therapeutic parameters. We developed a system to treat and online monitor PDT of skin cancer, using protoporphyrin-IX (PpIX) near-infrared fluorescence imaging. The system can be operated up to 150 mW/cm2 at 633 nm, with real-time fluorescence monitoring around 700 nm, using the treatment light itself for fluorescence excitation. This technology allows system portability, simplicity, and low cost. This study describes the system development and its comparison with a 400-450 nm commercial system to detect the PpIX fluorescence during a PDT in murine skin cancer model. The developed device was able to acquire considerably more fluorescence signal from deeper regions when compared to the violet excitation device.

Photodynamic therapy for skin cancer: How to enhance drug penetration?

Photodynamic therapy (PDT) induced by protoporphyrin IX (PpIX) has been widely used in dermatological practices such as treatment of skin cancers. Clearance rate depends on different factors such as light irradiation, skin oxygenation and drug penetration. The poor penetration of 5-aminolevulinic acid (5-ALA) with topical application is limited and restrains the production of PpIX which could restrict PDT outcomes. This review will focus on techniques already used to enhance drug penetration in human skin, and will present their results, advantages, and drawbacks. Chemical and physical pretreatments will be discussed. Chemical pre-treatments comprise of drug formulation modification, use of agents that modify the heme cycle, enhance PpIX formation, and the combination of differentiation-promoting agent prior to PDT. On the other hand, physical pretreatments affect the skin barrier by creating holes in the skin or by removing stratum corneum. To promote drug penetration, iontophoresis and temperature modulation are interesting alternative methods. Cellular mechanisms enrolled during chemical or physical pretreatments have been investigated in order to understand how 5-ALA penetrates the skin, why it is preferentially metabolized in PpIX in tumour cells, and how it could be accumulated in deeper skin layers. The objective of this review is to compare clinical trials that use innovative technology to conventional PDT treatment. Most of these pretreatments present good or even better clinical outcomes than usual PDT.

Simple and Selective HPLC-UV/Vis Bioanalytical Method to Determine Aluminum Phthalocyanine Chloride in Skin Permeation Studies.

Considering the feasibility of the aluminum phthalocyanine chloride (AlPcCl) application in the topical photodynamic therapy of cutaneous tumors and the lack of HPLC methods capable of supporting skin permeation experiments using this compound, the aim of this study was to obtain a simple and selective chromatographic method for AlPcCl determination in skin matrices. A HPLC-UV/Vis method was developed using a normal-phase column operating at 30°C, an isocratic mobile phase of methanol : phosphoric acid (0.01 M) at 1.5 mL/min, and detection at 670 nm. The method exhibited (i) selectivity against various contaminants found in the different skin layers, (ii) high drug extraction capacity from the hair follicle (>70%) and remaining skin (>80%), and (iii) low limits of detection and of quantification (0.03 and 0.09 μg/mL, resp.). The method was also linear in the range from 0.1 to 5.0 µg/mL (r = 0.9994) and demonstrated robustness with regard to experimental chromatographic parameters according to a factorial design. Lastly, the developed method was successfully tested in in vitro skin permeation studies of AlPcCl, proving its effectiveness in the development of pharmaceutical delivery systems containing this drug for topical photodynamic therapy of skin cancers.

Bacterial Cellulose Membranes as a Potential Drug Delivery System for Photodynamic Therapy of Skin Cancer

The development of drug delivery systems for photodynamic therapy (PDT) is increasingly demanded due to the hydrophobicity presented by most of photosensitizers molecules. Bacterial cellulose (BC), a highly pure cellulose produced by bacteria, possesses the essential features for applications in drug delivery systems, such as large surface area and excellent loading capacity. BC membranes prepared containing a photosensitizer, chloroaluminum phthalocyanine (ClAlPc), were tested aiming applications as a drug delivery system for PDT skin cancer protocols. BC membranes production was optimized regarding thickness and optical transmission. Thinner membranes lead to higher relative incorporation efficiencies. Skin permeation and retention in vitro tests were performed by using pig's ears as a skin model. ClAlPc was retained at stratum corneum and epidermis/dermis, showing adequate properties for topical administration of ClAlPc. Photophysical studies showed that singlet oxygen production was not affected for ClAlPc compartmentalized in the BC array. BC-ClAlPc membranes did not present cytotoxic effects in vitro.

Ambulatory photodynamic therapy of skin cancer

s / Photodiagnosis and Photodynamic Therapy 12 (2015) 325–375 331 concentrations. We show that with this additional constraint, the uncertainties of photochemical parameters can be reduced. http://dx.doi.org/10.1016/j.pdpdt.2015.07.028 Ambulatory photodynamic therapy of skin cancer I.D.W. Samuel1, O. Kulyk1, A. McNeill 1, H. Moseley2, J. Ferguson2, S. Ibbotson2 1 Organic Semiconductor Centre, SUPA, School of Physics and Astronomy, University of St Andrews, St Andrews KY16 9SS, UK 2 Photobiology Unit, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK Photodynamic therapy is an effective treatment for superficial non-melanoma skin cancers and pre-cancers. We report the development of wearable light sources for PDT, and also a camera used to measure the distribution of protoporphyrin IX, and clinical results of the use of these devices. Two factors limiting the widespread use of PDT are the availability of suitable light sources, and pain encountered by patients during treatment. Our work shows that recent advances in optoelectronics including organic light-emitting diodes provide an attractive path to compact wearable light sources, and sensors for medical applications. These light sources can be disposable and could remove the need for prolonged hospital visits for PDT. In addition to enabling convenient ambulatory treatment, they enable treatment to be delivered with lower light intensity for a longer time. Our clinical studies show that this approach leads to effective treatment and furthermore greatly reduces pain. Of 78 patientswith 124 lesions (mainly superficial basal cell carcinoma and Bowen’s disease), the median visual analogue (VAS) pain score for ambulatory PDT was 2 (range 0–9) comparedwith6 (range1–10) forhospital-basedconventional PDT. Seventy-eight patients with 87 lesions have been followed up to one year after treatment and clearance was seen in 79 patients (91%). We will also present results from a camera that quantitatively measures fluorescence from protoporphyrin IX, enabling its formation and distribution to studied. http://dx.doi.org/10.1016/j.pdpdt.2015.07.029 Computerized dosimetry planning for Vascular Targeted Photodynamic therapy with WST-11 for prostate cancer N. Betrouni1, S. Boukris2, B. Gaillac3, A.R. Azzouzi4, F. Benzaghou3 1 INSERM, U1189, Lille University Hospital, France 2 Device Department, Steba Biotech, Paris, France 3 Medical Department, Steba Biotech, Paris, France 4 University Hospital, Angers, France WST11 TOOKAD® Soluble is an intravascular photosensitizer drug administrated to patient in the operating room and activated by light diffusing optical fibers inserted transperineally inside the prostate under ultrasound guidance to target the focus. Phase 3 clinical trials ofWST11 are on-going. A drug dose (4mg/patient kg) wasdefinedasoptimal. It is activatedusingawavelengthof753nm. Light is delivered through cylindrical light diffusers at the rate of 0.15W/cm during 1333 s. The last issue that has to be solved is the determination of the light dose to be applied. It is expressed in term of light diffusers: number, lengths and positions inside the prostate gland. A first solutionwas introduced based on the resolution of the light diffusion equation. In this study,wepropose a novel approach. It presents the advantage of being fast and suitable for clinical conditions.Wehave defined amean actionmodel ofWST11 in prostate tissues by retrospective analysis of previous trials data. The model is applied in an optimization process to determine the light dose. Evaluation of the platform on clinical data showed that prediction of the therapy outcome was possible with an accuracy of 90%. http://dx.doi.org/10.1016/j.pdpdt.2015.07.030 Micro-vascular effects of photodynamic therapy in tumors evaluated with dynamic contrast-enhanced MRI Tom Schreurs, Gustav Strijkers, Holger Grull, Klaas Nicolay Biomedical Engineering Department, Eindhoven University of Technology, The Netherlands Tumor heterogeneity and complex dosimetry make prediction of PDT outcome challenging. Therefore, the aim of this studywas to use dynamic contrast-enhanced (DCE-)MRI for early monitoring of treatment efficacy. Mice with subcutaneous CT26 tumors received the photosensitizer Bremachlorin intravenously, activated 6h later by 655nm light. DCE-MRI, using Gd-DOTA, was performed before, 3h, and 24h after treatment. Tumor contrast enhancement and derived perfusion/permeability parameter Ktrans were spatially compared to histologically determined tissue viability. Viability staining showed that control tumors were largely viable. Treated tumors were mostly viable after 3h, but largely non-viable after 24h. DCE-MRI revealed that the average non-enhanced tumor fraction increased from 3.2% before PDT, to 24% after 3h, and 77% after 24h. The average Ktrans decreased from 0.25 to 0.09min−1 right after PDT. DCE-MRI could be used to visualize reduction in perfusion 3h after PDT, and nearly complete vascular shutdown after 24h. These effects could not be correlated to tumor viability yet, due to the lack of heterogeneity in the viability results. Additional experiments will be performed with milder treatment, to obtain more dispersion in viability. Previous results did suggest spatial correlation between remaining Gd-DOTA uptake after 24h, and tumor recurrence after multiple days. http://dx.doi.org/10.1016/j.pdpdt.2015.07.031 Performance characterization of a low-cost spatial frequency domain imaging system for the determination of optical properties in tissue-simulating phantoms and in vivo Arash Darafsheh, Emily A. Kraus, Michele M. Kim, Timothy C. Zhu, Jarod C. Finlay Department of Radiation Oncology, University of

Computerized dosimetry planning for Vascular Targeted Photodynamic therapy with WST-11 for prostate cancer

s / Photodiagnosis and Photodynamic Therapy 12 (2015) 325–375 331 concentrations. We show that with this additional constraint, the uncertainties of photochemical parameters can be reduced. http://dx.doi.org/10.1016/j.pdpdt.2015.07.028 Ambulatory photodynamic therapy of skin cancer I.D.W. Samuel1, O. Kulyk1, A. McNeill 1, H. Moseley2, J. Ferguson2, S. Ibbotson2 1 Organic Semiconductor Centre, SUPA, School of Physics and Astronomy, University of St Andrews, St Andrews KY16 9SS, UK 2 Photobiology Unit, University of Dundee, Ninewells Hospital, Dundee DD1 9SY, UK Photodynamic therapy is an effective treatment for superficial non-melanoma skin cancers and pre-cancers. We report the development of wearable light sources for PDT, and also a camera used to measure the distribution of protoporphyrin IX, and clinical results of the use of these devices. Two factors limiting the widespread use of PDT are the availability of suitable light sources, and pain encountered by patients during treatment. Our work shows that recent advances in optoelectronics including organic light-emitting diodes provide an attractive path to compact wearable light sources, and sensors for medical applications. These light sources can be disposable and could remove the need for prolonged hospital visits for PDT. In addition to enabling convenient ambulatory treatment, they enable treatment to be delivered with lower light intensity for a longer time. Our clinical studies show that this approach leads to effective treatment and furthermore greatly reduces pain. Of 78 patientswith 124 lesions (mainly superficial basal cell carcinoma and Bowen’s disease), the median visual analogue (VAS) pain score for ambulatory PDT was 2 (range 0–9) comparedwith6 (range1–10) forhospital-basedconventional PDT. Seventy-eight patients with 87 lesions have been followed up to one year after treatment and clearance was seen in 79 patients (91%). We will also present results from a camera that quantitatively measures fluorescence from protoporphyrin IX, enabling its formation and distribution to studied. http://dx.doi.org/10.1016/j.pdpdt.2015.07.029 Computerized dosimetry planning for Vascular Targeted Photodynamic therapy with WST-11 for prostate cancer N. Betrouni1, S. Boukris2, B. Gaillac3, A.R. Azzouzi4, F. Benzaghou3 1 INSERM, U1189, Lille University Hospital, France 2 Device Department, Steba Biotech, Paris, France 3 Medical Department, Steba Biotech, Paris, France 4 University Hospital, Angers, France WST11 TOOKAD® Soluble is an intravascular photosensitizer drug administrated to patient in the operating room and activated by light diffusing optical fibers inserted transperineally inside the prostate under ultrasound guidance to target the focus. Phase 3 clinical trials ofWST11 are on-going. A drug dose (4mg/patient kg) wasdefinedasoptimal. It is activatedusingawavelengthof753nm. Light is delivered through cylindrical light diffusers at the rate of 0.15W/cm during 1333 s. The last issue that has to be solved is the determination of the light dose to be applied. It is expressed in term of light diffusers: number, lengths and positions inside the prostate gland. A first solutionwas introduced based on the resolution of the light diffusion equation. In this study,wepropose a novel approach. It presents the advantage of being fast and suitable for clinical conditions.Wehave defined amean actionmodel ofWST11 in prostate tissues by retrospective analysis of previous trials data. The model is applied in an optimization process to determine the light dose. Evaluation of the platform on clinical data showed that prediction of the therapy outcome was possible with an accuracy of 90%. http://dx.doi.org/10.1016/j.pdpdt.2015.07.030 Micro-vascular effects of photodynamic therapy in tumors evaluated with dynamic contrast-enhanced MRI Tom Schreurs, Gustav Strijkers, Holger Grull, Klaas Nicolay Biomedical Engineering Department, Eindhoven University of Technology, The Netherlands Tumor heterogeneity and complex dosimetry make prediction of PDT outcome challenging. Therefore, the aim of this studywas to use dynamic contrast-enhanced (DCE-)MRI for early monitoring of treatment efficacy. Mice with subcutaneous CT26 tumors received the photosensitizer Bremachlorin intravenously, activated 6h later by 655nm light. DCE-MRI, using Gd-DOTA, was performed before, 3h, and 24h after treatment. Tumor contrast enhancement and derived perfusion/permeability parameter Ktrans were spatially compared to histologically determined tissue viability. Viability staining showed that control tumors were largely viable. Treated tumors were mostly viable after 3h, but largely non-viable after 24h. DCE-MRI revealed that the average non-enhanced tumor fraction increased from 3.2% before PDT, to 24% after 3h, and 77% after 24h. The average Ktrans decreased from 0.25 to 0.09min−1 right after PDT. DCE-MRI could be used to visualize reduction in perfusion 3h after PDT, and nearly complete vascular shutdown after 24h. These effects could not be correlated to tumor viability yet, due to the lack of heterogeneity in the viability results. Additional experiments will be performed with milder treatment, to obtain more dispersion in viability. Previous results did suggest spatial correlation between remaining Gd-DOTA uptake after 24h, and tumor recurrence after multiple days. http://dx.doi.org/10.1016/j.pdpdt.2015.07.031 Performance characterization of a low-cost spatial frequency domain imaging system for the determination of optical properties in tissue-simulating phantoms and in vivo Arash Darafsheh, Emily A. Kraus, Michele M. Kim, Timothy C. Zhu, Jarod C. Finlay Department of Radiation Oncology, University of

Fluorescent Monitoring of Photodynamic Therapy for Skin Cancer in Clinical Practice

The aim of the investigation was to assess the fluorescent imaging capabilities to monitor photodynamic therapy (PDT) of non-melanoma skin cancer, and study the correlation of PS (photosensitizer) fluorescence value (accumulation and photobleaching rate) and efficacy of the treatment provided. Materials and Methods. The study was conducted in the Nizhny Novgorod Regional Oncologic Hospital. We analyzed fluorescent images and PDT outcomes in 226 patients with non-melanoma skin carcinomas. Results. The assessment of short-term treatment results revealed the relationship between PS photobleaching and tumor complete response rate: a complete response was found in 89% cases in complete photobleaching, in 87% cases — in partial photobleaching, and in 81% — in no photobleaching (p>0.05). However, we found no effect of PS accumulation rate on complete response rate. The analysis of long-term results with significant difference (p=0.044) showed tumor recurrence rate in low PS concentration (tumor/norm) to be 9.5%, while in moderate and high concentrations the recurrence rate appeared to be 4.1%. There was revealed the tendency for recurrence rate increase — 10.4% with no PS photobleaching versus 4.4% in PS complete and partial photobleaching (p=0.051). The patients with high accumulation rate and complete PS photobleaching had the best clinical findings, the observation period being from 4 to 40 months. Conclusion. Fluorescent monitoring enables to maintain noninvasive control of PS accumulation and photobleaching that can contribute to the selection of individual laser exposure parameters. It is reasonable to develop multimodal bioimaging for follow-up real-time monitoring of basic photodynamic reactions and treatment results.

Update on topical photodynamic therapy for skin cancer

Topical photodynamic therapy has become an established therapy option for superficial non-melanoma skin cancers with a substantial evidence base. In this update the increased choice in photosensitizers and light sources are reviewed as well as novel protocols to move beyond lesional treatment and address field therapy. Daylight PDT is emerging as an alternative to conventional office/hospital-based PDT that offers the advantage of much reduced pain. Although most studies have assessed efficacy of PDT in immune-competent patients, there is accumulating evidence for topical PDT being considered an option to assist in reducing the skin cancer burden in organ transplant recipients. The fluorescence associated with photosensitizer application can help delineate lesions prior to full treatment illumination and offers a useful adjunct to treatment in patients where diagnostic uncertainty or poor lesion outline complicates clinical care. PDT may also offer significant benefit in delaying/preventing new cancer development and combined with its recognized photo-rejuvenating effects, is emerging as an effective therapy capable of clearing certain superficial skin cancers, potentially preventing new lesions as well as facilitating photo-rejuvenating effects in treated areas.

Applications of Natural Compounds in the Photodynamic Therapy of Skin Cancer

Despite significant advances in early diagnosis and treatment, skin cancer is one of the leading causes of death. Photodynamic therapy (PDT) is a new therapeutic modality that is emerging as an important resource against malignant tumors. This strategy is based on the action of photosensitizers, i.e. of molecules which may accumulate preferentially inside tumor cells where they exert a cytotoxic effect after excitation by light at appropriate wavelengths. Some forms of skin cancers and also some non-tumor pathologies are now treated with PDT. Several compounds with photosensitizing activity have been identified, and some of these molecules are commercially available. Many photoactive principles are natural compounds. Numerous reviews in the last decade have focused on photodynamic therapy, its effects and applications, but less attention has been paid to plant extracts or molecules of natural origin studied for their phototoxic activity to date.This review critically examines the potential role of various plant extracts and naturally occurring compounds in the treatment of skin cancer. Both in vitro and in vivo effects of these agents, together with their known related cellular and molecular mechanisms, are presented and discussed.

PLGA Nanoparticles as Delivery Systems for Protoporphyrin IX in Topical PDT: Cutaneous Penetration of Photosensitizer Observed by Fluorescence Microscopy

Poly(D,L lactic-co-glycolic acid) (PLGA) based nanoparticles (NPs) are proposed for topical delivery of Protoporphyrin IX (PpIX) in Photodynamic Therapy of skin cancers. PpIX loaded into PLGA NPs showed nanometric average diameter (-280 nm), spherical forms and pH - 5.7, conditions suitable for topical application. In vitro release of PpIX from NPs was sustained up to 24 hr with a burst release effect of about 37.0% at 2 hr. Penetration and distribution of PpIX in hairless mice skin was determined by fluorescence microscopy 8 or 24 hrs after application of PpIX-NPs in the animals. At 24 hours, areas located in deeper regions of the skin were found to have greater fluorescence intensity. The finding indicates a localized effect of PpIX-NPs in the epidermis plus dermis--a site of action for topical PDT--and suggests a potential use of PpIX-NPs in PDT associated to skin cancer treatments.

Nanoparticles of Lyotropic Liquid Crystals: A Novel Strategy for the Topical Delivery of a Chlorin Derivative for Photodynamic Therapy of Skin Cancer

Nanoparticles of lyotropic liquid crystals loaded with a new photosensitizer (a chlorin derivative) were developed for use in photodynamic therapy (PDT). These systems were characterized by spectrofluorimetric, dynamic light scattering, and small angle X-ray diffraction (SAXRD) analyses. In vitro and in vivo penetration studies in animal models were performed using animal model membranes. The systems had a particle size of 161 ± 4 nm and a polydispersity index of 0.175 ± 0.027. Furthermore, SAXRD studies demonstrated that the preparations remained in the liquid crystalline phase type hexagonal after drug loading. The encapsulation rate was higher than 50%, and cell viability studies revealed that the nanodispersion is not harmful for L929 skin cells. In vitro and in vivo penetration studies confirmed that the nanodispersion of hexagonal phase enabled a higher drug skin uptake compared to the control. Additionally, a fluorescence microscopy study demonstrated a higher biodistribution of the chlorin derivative in the skin layers of hairless mice compared to the control. Taken together, the results show the potential of this nanodispersion for the delivery of the photosensitizer into the skin, which is a crucial condition for successful topical PDT. Keywords: Photodynamic Therapy, skin delivery, chlorin, nanoparticles, liquid crystal.

Optical coherence tomography-guided photodynamic therapy for skin cancer: case series

Optical coherence tomography-guided photodynamic therapy for skin cancer: case series

Optical coherence tomography-guided photodynamic therapy for skin cancer: Case series

Optical coherence tomography-guided photodynamic therapy for skin cancer: Case series

Quantitative fluorescence imaging of protoporphyrin IX through determination of tissue optical properties in the spatial frequency domain

The ability to quantitatively determine tissue fluorescence is of interest for the purpose of better understanding the details of photodynamic therapy of skin cancer. In particular, we are interested in quantifying protoporphyrin IX (PpIX) in vivo. We present a method of correcting fluorescence for effects of native tissue absorption and scattering properties in a spatially resolved manner that preserves the resolution of the fluorescence imaging system, based off a homogeneous representation of tissue. Validation was performed using a series of liquid turbid phantoms having varying concentrations of absorber, scatterer, and fluorophore (PpIX). Through the quantification of tissue optical properties via spatial frequency domain imaging, an empirical model based on Monte Carlo simulations was deployed to successfully decouple the effects of absorption and scattering from fluorescence. From this we were able to deduce the concentration of the PpIX to within 0.2 μg/ml of the known concentration. This method was subsequently applied to the determination of PpIX concentration from in vivo normal skin where the model-based correction determined a concentration of 1.6 μg/ml, which is in agreement with literature.