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.     

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.     

Aminoleveulinate photodynamic therapy (ALA-PDT) for Bowen’s disease in a SLE patient: Case report and literature review

We reported a rare case of topical 5-aminolevulinic acid (ALA)–photodynamic therapy (PDT) in the treatment of a systemic lupus erythematosus (SLE) patient with lower limb multiple Bowen’s disease (BD). At the end of the treatment, an excellent clinical response was observed and no recurrence of rash after 2 months of treatment. The recovery time was prolonged only after the first treatment, however, no photosensitive phenomena were observed during and after the treatment. This is the first report to describe ALA-PDT for patient-confirmed photosensitivity in an Asian patient. Whether PDT is contraindicated for SLE remains to be discussed, although our findings show that PDT can be used as an alternative therapy for SLE patients with BD who cannot tolerate surgery.     

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.     

Extramammary Paget''s disease treated with topical and systemic photodynamic therapy

Surgical excision and radiotherapy for extramammary Paget's disease (EMPD) at specific sites such as the groin and genitalia is often inappropriate. An 80-year-old man with histologically proven EMPD of the left groin and scrotum was referred for PDT.

The lesion and normal skin thickness were measured by a 20 MHz, two-dimensional ‘B’ ultrasound scanner (US).

δ-5-Aminolaevulinic acid (ALA), was applied followed 6 h later by irradiation using a filtered xenon-arc lamp. Clinical improvement was apparent four weeks after first PDT session with a reduction in ulceration and lesion size and moderate thickness reduction on US. Superficial ulceration recurred 9 months after the fifth treatment. This recurrence was treated with intravenously administered porfimer sodium. This, followed by one topical PDT treatment resulted in significant clinical and US cure and the patient remains disease free at 1-year follow-up.     

Photodynamic therapy in dermatology: Dundee clinical and research experience

Topical photodynamic therapy (PDT) is increasingly accepted and used as a highly effective treatment for superficial non-melanoma skin cancer and dysplasia. We describe the developments in topical PDT for the treatment of skin diseases in our own PDT Centre in Dundee, both clinically and from a research base. Improvements in PDT could be achieved by optimisation of photosensitiser and light delivery, and these goals underpin the aims of our centre. We hope to facilitate the dissemination of use of PDT in dermatology throughout Scotland and outline some of the progress in these areas.     

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.     

Photodynamic therapy and pain: A systematic review

Photodynamic therapy (PDT) is an effective treatment for actinic keratoses and early skin cancers, and the only office procedure to control field cancerization. Procedure-associated pain limits widespread PDT use and by early termination of treatment can decrease overall therapeutic efficacy. Here we review and assess reported interventions on PDT-associated pain, in order to identify the most promising methods to manage treatment-associated pain and identify focus for future studies. Literature search was performed using MEDLINE, EMBASE, and the Cochrane Library by two independent reviewers to select publications that assessed and compared pain quantitatively during PDT treatment for actinic keratoses, basal cell carcinomas, and/or in situ squamous cell carcinomas. A total of 48 studies reporting on pain during PDT were identified and were comprised of two main categories of interventions: pain-controlling therapies and PDT parameter (photosensitizer or photo-irradiation) adjustments. Of these interventions: nerve block, subcutaneous infiltration anesthesia, cold analgesia, and transcutaneous electrical nerve stimulation, but not topical anesthetic gels, were associated with less PDT-related pain; 5-aminolevulinic acid (ALA) tended to be more painful than methyl-5-aminolevulinate (MAL); daylight PDT was less painful than conventional PDT; and lower irradiance delivery produced lower pain scores in general. There is no single crystalized protocol for management of PDT-related pain. Evidence suggests that continuous activation of low levels of PpIX with methods using lower irradiance and possibly shorter incubation times are associated with decreased pain without loss of PDT efficacy. Protocols to reduce pain should be standardized and large controlled trials are needed.     

Photodynamic therapy in Argentina

The use of endogenous Protoporphyrin IX generated through the heme biosynthetic pathway after administration of 5-aminolevulinic acid (ALA) has led to many applications in photodynamic therapy (PDT). In Buenos Aires, Argentina, the Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), reported for the first time, in 1975, porphyrin synthesis from ALA in highly dividing plant tissues. Increased porphyrin synthesis in tumours as well as cell photosensitisation was reported soon after. Our group is also interested in studying the use of new synthetic lipophilic derivatives of ALA as well as ALA delivery in liposomes. We have elucidated the mechanism of ALA transport in mammalian and yeast cells. The interactions between ALA-PDT and nitric oxide were investigated in three murine adenocarcinoma cell lines. In the National University of Río Cuarto, Córdoba, a group is devoted to the synthesis of new porphyrin-derived photosensitisers to study their effects on photoinactivation of bacterial and mammalian cells death by PDT. At the Centre of Electron Microscopy of the Cordoba National University, a prototype of a 630 nm noncoherent light source was designed and constructed. Cost of the light source and scarce knowledge of the benefits of PDT by physicians limit the spread of the treatment throughout the country.     

Inflammation burst after 5-aminolevulinic acid-photodynamic therapy for the treatment of actinic keratosis complicating rosacea: A case report

A 72-year-old woman suffering from multiple actinic keratosis (AK) complicating steroid-induced rosacea received 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) in our outpatient clinic. Both AKs and rosacea achieved remission after one session of PDT. However, an adverse effect of severe acute inflammatory response emerged with lasting hyperpigmentation. We then terminated the following PDT sessions . After skin care and close follow-up for a half year, most symptoms and lesions of AK and rosacea disappeared with mild hyperpigmentation left. ALA-PDT is commonly recommended for multiple AKs based on effectiveness and noninvasiveness, but has controversial efficacy and safety for rosacea. The unusual excessive inflammation in this patient after ALA-PDT may due to skin barrier destruction, vasomotor dysfunction and the immune response by dead Demodex after PDT. This case indicated that carefully evaluation before ALA-PDT is of great importance, especially for those patients with complicated skin situation. For AKs complicating rosacea, modified parameters of ALA-PDT such as less ALA incubation time or reduced light dose should be further studied to achieve the optimal efficacy and safety of ALA-PDT and offer the best benefit.     

光动力疗法与热损伤对正常大鼠胃损伤的研究

为了初步探讨ＰＤＴ与热损伤对正常胃损伤作用机制的差异，本实验以血卟啉衍生物及氩离子泵染料激光器为光敏剂及光源，观察了大鼠胃壁在单纯氩离子激光照射和ＰＤＴ时，照射部位的温度及组织学在照射后７２小时和二周的改变。结果：氩离子激光照射组和ＰＤＴ组胃壁温度均高于对照组（Ｐ＜０．０１），但ＰＤＴ组温度均低于３７℃。氩离子激光照射后的胃壁组织在７２小时各层组织均明显出血，炎细胞浸润，组织凝固坏死。电镜下见胶原纤维肿胀，排列紊乱，甚至溶解吸收。二周后损伤部位以纤维瘢痕组织修复。ＰＤＴ组在７２小时胃壁组织也有充血和炎细胞浸润，但仅有轻度组织坏死，损伤深度未超过粘膜下层。电镜下见胶原纤维结构基本正常。二周后损伤部位以组织再生修复，未留瘢痕。结论：ＰＤＴ与氩离子激光组织损伤及修复方式不同，ＰＤＴ不损伤胃粘膜下胶原纤维。     

Barrett's oesophagus and photodynamic therapy (PDT)

Barrett's oesophagus is a precursor of oesophageal adenocarcinoma. This cancer has the fastest growing incidence of any solid tumour in the Western world. Surveillance of Barrett's oesophagus is routinely undertaken to detect early malignant transformation. However, ablative endoscopic treatments are available and these can obliterate the abnormal epithelium, allowing neo-squamous re-growth. Photodynamic therapy (PDT) using haematoporphyrin derivative (HpD)/porfimer sodium (Photofrin^®), m-tetrahydroxyphenyl chlorin (mTHPC) and 5-aminolaevulinic acid (ALA) utilise such a technique. In this non-thermal method of ablation, the photosensitisers, together with light and oxygen, produce local tissue destruction. The use of PDT ablation of Barrett's oesophagus is reviewed.     

Photodynamic therapy (PDT) - Initiation of apoptosis via activation of stress-activated p38 MAPK and JNK signal pathway in H460 cell lines

Aims

The purpose of this study was to investigate the photoefficacies of protoporphyrin IX (PpIX) generated by drug precursor 5-aminolevulinic acid (ALA) and its hexyl ester (H-ALA) on two human non-small lung carcinoma cell lines (H460/Bcl-2 and H460/neo).

Main methods

Drug uptake and the photoefficacies of PpIX were measured by flow cytometry and MTT assay; while the mode of cell death and alternation of signal transduction pathways were studied with 4′,6-diamidino-2-phenylindole (DAPI) staining and Western blot analysis, respectively.

Key findings

The flow cytometric analysis of H-ALA (5 μM) uptake revealed optimal fluorescent intensity at 8 h incubation, while ALA (0.5 mM) was still far from saturation. The LD₃₀ of H-ALA-PDT was 30 μM, 2 J/cm², while the LD₃₀ of ALA-PDT was 3 mM, 2 J/cm². The dark toxicities mediated by both pro-drug H-ALA and ALA were negligible. By DAPI staining, apoptotic cell death was observed. In addition, by Western blot analysis, H-ALA- and ALA-mediated PDT initiated apoptotic cell death via the up-regulation and activation of p38 mitogen activated protein kinase (MAPK), the stress-activated c-jun N-terminal kinases (JNK) and ERK.

Significance

These results suggested that H-ALA and ALA mediated PDT displayed similar photocytotoxicities towards the two non-small lung cancer cells. Our present study also demonstrates H-ALA or ALA mediated PDT in H460 cells are closely related to the activation of p38 MAPK and JNK signalling pathway.     

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.     

Sandpaper curettage: A simple method to improve PDT outcomes for actinic keratosis

INTRODUCTIONPhotodynamic therapy (PDT) is a non-scarring, repeatable, and safe treatment for actinic keratosis (AK), but improvements in efficacy are still needed.BACKGROUNDDevices such as steel blades, needle rollers, and lasers are currently used to remove hypertrophic stratum corneum on AKs to improve PDT outcomes. However, curettage with fine sandpaper could be a gentler, effective alternative.METHODSA retrospective study was designed to compare PDT with or without sandpaper curettage. Patients were selected from a database registry of patients with face and scalp AKs (ClinicalTrials.gov NCT03319251). Patients in Group 1 underwent PDT alone (20% ALA, 15 min; blue light 417 nm, 30 min). Patients in Group 2 were pretreated with gentle sandpaper curettage prior to ALA and illumination. The two groups were compared using multivariate matching, normalizing for age, sex, initial AK counts, and time to follow-up.RESULTSSixty-six patients were selected for matching analysis (n=38, PDT only; n=28, PDT+curettage). Demographics between the groups were similar (mean ± SD), including age (71.0 ± 8.3 vs. 71.0 ± 8.0 years), baseline AK count (53 ± 39 vs. 44± 32), and time to post-PDT follow-up (111 ± 28 vs. 113 ± 32 days). At follow-up, patients who received curettage showed an overall 55% improvement in scalp AK clearance compared to patients who did not receive curettage, adjusting for sex, age, time to follow-up, and baseline AK count (p = 0.0322, multivariable linear regression).DISCUSSIONSandpaper curettage before PDT treatment is an easy and inexpensive method to significantly improve AK clearance rates.     

Chlorin e6-mediated photodynamic therapy promotes collagen production and suppresses MMPs expression via modulating AP-1 signaling in P. acnes-stimulated HaCaT cells

BackgroundPhotodynamic therapy (PDT) is a clinically approved therapeutic for cancers and non-neoplastic diseases, based on the use of a photosensitizer activated by light. The feasibility of PDT depends on several factors, such as PDT dose, photosensitizer efficacy, type of light source, and target tissue irradiated.MethodsIn this study, the second generation photosensitizer chlorin e6 (Ce6) and halogen light were used to investigate their PDT effect on the collagen production and MMPs expression of heat killed P. acnes-stimulated HaCaT cells. The mRNA levels of COL1A1, c-Jun, and c-Fos were detected by RT-PCR. The protein levels of MMPs, ERK and JNK were detected by western blot. The transactivation of AP-1 was detected by luciferase assay.ResultsCe6-based PDT markedly upregulated the mRNA level of COL1A1 and type I procollagen level; and at the same time downregulated the expression of MMPs in P. acnes-infected HaCaT cells. Moreover, Ce6-mediated PDT, in a dose dependent manner, inhibited P. acnes-induced phosphorylation of JNK and ERK, as wells as the phosphorylation of their downstream targets c-Jun and c-Fos. P. acnes-induced mRNA expression of c-Jun and c-Fos were also suppressed by Ce6-mediated PDT. The transactivation of AP-1 induced by P. acnes infection was also downregulated.ConclusionThese results indicated that Ce6-mediated PDT with halogen light enhanced collagen production, but inhibited the expression of MMPs in P. acnes-infected HaCaT cells, by regulating AP-1 signals. This investigation provided the first molecular basis for the increase in collagen production by Ce6-mediated PDT, suggesting its potential use for scar amelioration and skin rejuvenation in acne treatment.     

No room for pain: A prospective study showing effective and nearly pain-free treatment of actinic keratosis with simulated daylight photodynamic therapy (SDL-PDT) using the IndoorLux® System in combination with BF-200 ALA (Ameluz®)

BackgroundPhotodynamic therapy (PDT) with natural daylight is effective and less painful than conventional PDT when treating actinic keratosis (AK), however its weather dependency is restrictive. This prospective open-label observational single-arm study examined efficacy and safety of simulated daylight (SDL)-PDT using the IndoorLux® system in combination with 5-aminolevulinic acid gel (BF-200 ALA).Methods12 patients with mild/moderate AK on the face or scalp received two SDL-PDTs. BF-200 ALA was applied prior to a 2 h illumination with the IndoorLux® System. Patients evaluated pain during and after SDL-PDT on visual analogue scales (VAS). Primary endpoint was lesion count reduction three months after the second SDL-PDT. Secondary endpoint was pain during and after illumination.ResultsMedian individual clearance rate was 83.75% (66.7–100.0%); 33.3% of the patients and 84.9% of the lesions were completely cleared. Median size of the remaining partially cleared lesions decreased by 42.9%. The first SDL-PDT was pain-free for 7 patients (58.3%, VAS=0). Median VAS during and after the first treatment was 0 (0.0–0.3). For the second SDL-PDT, median VAS was 0.1 (0.0–5.5, during) and 0 (0.0–4.5, after). Both SDL-PDTs were pain-free for 6 patients.ConclusionSDL-PDT was effective and nearly pain-free, emphasizing its advantages and potential for common practice.     

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.     

Topical photodynamic therapy with 5-aminolevulinic acid for cervical high-risk HPV infection

ObjectiveTo investigate the clinical efficacy of 5-aminolevulinic acid photodynamic therapy (ALA–PDT) for cervical high-risk HPV (HR-HPV) infection.MethodsIn this prospective study, a total of 76 patients with persistent cervical HR-HPV infection were randomly divided into two groups. The treatment group (39 patients) received three treatments of ALA–PDT at two-week intervals. The control group (37 patients) received no treatment. All patients were followed up for 9 months. Hybrid Capture HPV DNA Assay and ThinPrep cytology test (TCT) were performed for both groups. Patients with abnormal TCT results received colposcopic biopsy before treatment and during follow-ups.ResultsHR-HPV remission rates were 64.10% (25/39) in the treatment group and 24.32% (9/37) in the control group at 3 month follow-up. Complete remission rates were 76.92% (30/39) and 32.40% (12/37), respectively, in the two groups at 9 month follow-up. There was a statistically significant difference between the two groups (P < 0.01). Conversion rates of abnormal TCT results were 81.81% (9/11) in the treatment group and 12.50% (1/8) in the control group at 3 months, and 90.90% (10/11) and 25.00% (2/8), respectively, at 9 months. Five of six patients with CIN I in the treatment group and no patients in the control group achieved complete response at 9 months. There was a statistically significant difference between the two groups (P < 0.01).ConclusionTopical ALA–PDT is an effective, safe and well tolerated treatment for cervical HR-HPV infection.     

Photodynamic therapy effective for the treatment of actinic keratosis and basal cell carcinoma in bullous pemphigoid patients

Treating skin cancers and extensive actinic keratosis in patients with bullous pemphigoid (BP) can be challenging. Treatment options pose unique risks in these patients as surgical wounds can have delayed wound healing and photodynamic therapy (PDT) may exacerbate their blistering disease. We report the successful use of PDT to treat actinic keratosis and skin cancers in two patients with BP, both of whom had excellent response to PDT and tolerated treatment without any bullous disease flares. Carefully selected patients with skin cancers and stable, well controlled BP can be safely considered for treatment using PDT.