Treatment of Recalcitrant Viral Warts with Photodynamic Therapy with Mal and Red Light

Background: Photodynamic therapy (PDT) is a treatment for non-melanoma skin cancer. In recent years, its use has expanded to new indications. Viral warts (VW) are some of the most promising. Methods: A retrospective, descriptive, observational study was carried out. Patients who did not respond to cryotherapy were selected and were occluded with methyl aminolevulinate (MAL) for three hours and they were illuminated with red light. Tolerance to treatment was evaluated using a visual analog scale for pain (from 0 to 10). Results: A total of 15 patients with 134 VW were treated. A complete response was obtained in 13 of 15 patients (87%) and in 127 of 134 lesions (95%). The mean number of sessions was 3.1 (range 1 to 6) and the average pain score was 3.1 (range 0 to 8). Conclusions: PDT is a treatment that offers good results in the treatment of VW that are resistant to routine treatment. The treatment was well tolerated in our patient group.

Deep near infrared light-excited stable synergistic photodynamic and photothermal therapies based on P-IR890 nano-photosensitizer constructed via a non-cyanine dye

The cyanine dyes represented by IR780 can achieve synergistic photodynamic therapy(PDT)and photothermal therapy(PTT)under the stimulation of near-infrared(NIR)light(commonly 808 nm).Unfortunately,the stability of NIR-excited cyanine dyes is not satisfactory.These cyanine dyes can be attacked by self-generated reactive oxygen species(ROS)during PDT processes,resulting in structural damage and rapid degradation,which is fatal for phototherapy.To address this issue,a novel non-cyanine dye(IR890)was elaborately designed and synthesized by our team.The maximum absorption wavelength of IR890 was located in the deep NIR region(ca.890 nm),which was beneficial for further improving tissue penetration depth.Importantly,IR890 exhibited good stability when continuously illuminated by deep NIR light.To improve the hydrophilicity and biocompatibility,the hydrophobic IR890 dye was grafted onto the side chain of hydrophilic polymer(POEGMA-b-PGMA-g-C≡CH)via click chemistry.Then,the synthesized POEGMA-b-PGMA-g-IR890 amphiphilic polymerwas utilized to prepare P-IR890 nano-photosensitizer via self-assembly method.Under irradiation with deep NIR light(850 nm,0.5 W/cm^(2),10 min),the dye degradation rate of P-IR890 was less than 5%.However,IR780 was almost completely degraded with the same light output power density and irradiation duration.In addition,P-IR890 could stably generate a large number of ROS and heat at the same time.It was rarely reported that the stable synergistic combination therapy of PDT and PTT could be efficiently performed by a single photosensitizer via irradiation with deep NIR light.P-IR890 exhibited favorable anti-tumor outcomes through apoptosis pathway.Therefore,the P-IR890 could provide a new insight into the design of photosensitizers and new opportunities for synergistic combination therapy of PDT and PTT.

Photodynamic therapy of oral leukoplakia and orallichen planus using methylene blue:A pilot study

Premalignant lesions like oral lichen planus(OLP),oral leukoplakia(OL)has a fair probability of transforming into malignancy and they are perverse toward conventional therapies.Photody-namic therapy(PDT)has been considered as an alternative/complimentary therapeutic mo-dality for the management of premalignant lesions.In this study,methylene blue mediated photodynamic therapy(MB-PDT)was used as a possible alternative method for the treatment of OLP and OL.A total of 15 OLP lesions and 13 OL lesions were enrolled in the study.The patients were irradiated 1using metal halide lamp filtered at 630土10nm,with a light exposure dose of 120 J/cm^(2) per stting.For the OLP lesions,MB-PDT was performed once a week for four weeks and for the OL lesions,MB-PDT was performed twice a week for three weeks.Lesions were evaluated pre-and post-and at follow-u sessions by changes in sign and symptom scores,and size of lesions.We have observed a 53.3%of complete reduction in the treated OLP lesions and their decrease in size,sign and symptom score after treatment and at follow-up session was statistially signifcant.We have also observed complete response for one OL lesion of the 13 treated lesions.The result indicates that MB-PDT is an effective modality in management of OLP and OL.Among the two types of premalignancies treated with MB-PDT,OLP lesions responded much better than that of OL.

Toluidine blue O and porphyrin-mediated photodynamic therapy on three main pathogenic bacteria of periodontitis using portable LED phototherapy device

Photodynamic therapy(PDT)has been commonly used in treating many diseases,such as cancer and infectious diseases.We investigated the different effects of PDT on three main pathogenic bacteria of periodontitis-Prevotella melaninogenica(P.m.),Porphyromonas gingitvalis(P.g.)and Aggregatibacter actinomycetercomitans(A.a-).The portable red light-ermitting diode(LED)phototherapy device was used to assess the exogenous PDT effects with different light doses and photosensitizer concentrations(Toluidine blue O,TBO).The portable blue LED phototherapy device was used to assess the endogenous PDT effects with the use of endogenous photosensit izers(porphyrin)under dfferent light doses.We found out that both exogenous and endogenous PDT were able to restrict the growth of all the three bacteria significantly.Moreover,the optimal PDT conditions for these bacteria were obtained through this in vitro screening and could guide the clinical PDT on periodontitis.

Potential of photodynamic therapy in the management of infectious oral diseases

Photodynamic therapy(PDT)can take place in the presence of three elements:Light with an appropriate wavelength;a photosensitizer;and the presence of oxygen.This type of treatment is very effective overall against bacterial,viral and mycotic cells.In the last 10 years many papers have been published on PDT with different types of photosensitizers(e.g.,methylene blue,toluidine blue,indocyanine green,curcumin-based photosensitizers),different wavelengths(e.g.,460 nm,630 nm,660 nm,810 nm)and various parameters(e.g.,power of the light,time of illumination,number of sessions).In the scientific literature all types of PDT seem very effective,even if it is difficult to find a standard protocol for each oral pathology.PDT could be an interesting way to treat some dangerous oral infections refractory to common pharmacological therapies,such as candidiasis from multidrug-resistant Candida spp.

Indocyanine Green-Conjugated Magnetic Prussian Blue Nanoparticles for Synchronous Photothermal/Photodynamic Tumor Therapy

Indocyanine green(ICG) is capable of inducing a photothermal effect and the production of cytotoxic reactive oxygen species for cancer therapy. However, the major challenge in applying ICG molecules for antitumor therapy is associated with their instability in aqueous conditions and rapid clearance from blood circulation,which causes insufficient bioavailability at the tumor site.Herein, we conjugated ICG molecules with Prussian blue nanoparticles enclosing a Fe_3O_4 nanocore, which was facilitated by cationic polyethyleneimine via electrostatic adsorption. The nanocarrier-loaded ICG formed stable aggregates that enhanced cellular uptake and prevented fluorescence quenching. Moreover, the strong superparamagnetism of the Fe_3O_4 core in the obtained nanocomposites further improved cellular internalization of the drugs guided by a localized magnetic field. The therapeutic efficacy of this nanoplatform was evaluated using tumor models established in nude mice, which demonstrated remarkable tumor ablation in vivo due to strong photothermal/photodynamic effects. This study provides promising evidence that this multifunctional nanoagent might function as an efficient mediator for combining photothermal and photodynamic cancer therapy.

Novel intense pulsed light-photodynamic therapy strategy in the treatment of facial actinic keratoses concomitant with rosacea

Rosacea presents as transient or persistent erythema,papules,pustules,fAushing,and telangi-ectasia on the middle of the face,which has some clinical similarity with act inic keratosis(AK).These two conditions can coexist in the same patient.Dermoscopy and reflect ance confocal microscopy(RCM)could be useful methods for diagnosis and monitoring treatment efficacy.Novel intense pulsed light-photodynamic therapy(IPL-PDT)may have better tolerance and curative effect than traditional red-light 5-aminolevulinic acid photodynamic therapy(ALA-PDT).Herein,we present a case of facial AKs concomitant with rosacea where combination therapy of novel IPL-PDT and oral minocycline was effective in that AK lesions were eliminated and the patient's facial erythema and telangiectasia were significantly improved.

Implementation and uniformity calibration of LED array for photodynamic therapy

Irradiance uniformity is an important parameter for a Photodynamic Therapy(PDT)device.The calibration and verification of a LED array light source based on computer vision technology were implemented and carried out.First,the correlation coe±cients between the pulse width modulate value and the irradiance were calibrated.Then,the correction of the actual light center and divergence angle were solved by image processing to reduce errors from each LED lens.Finally,uniformity was optimized according to the irradiance formula of the Lambertian source.The lowest coe±cients of variation of irradiance were 4.87%in a 5 cm×12 cm area and 3.55%in a 3 cm×10 cm area within the depth range of 8–12 cm when the expected irradiance was 100 mW/cm^(2).This finding indicated that the light source can achieve a more uniform illumination and provide a better therapeutic effect for the PDT of port-wine stains.

Highly Selective Photodynamic Therapy with a Short Drug-Light Interval Using a Cytotoxic Photosensitizer Porphyrus Envelope for Drug-Resistant Prostate Cancer Cells

Background: Photodynamic therapy (PDT) is a less invasive cancer treatment using photochemical reactions induced by light irradiation to a photosensitizer (PS). Highly selective PDT with fast accumulation of the PS in target site might be a promising treatment option for drug-resistant prostate cancer facing high incidence rate of elderly men who have no effective treatment options and require a minimally invasive treatment. Hemagglutinating virus of Japan envelope (HVJ-E) allows selective and fast drug delivery to the drug-resistant prostate cancer cells via rapid cell membrane fusion. PS named porphyrus envelope (PE) has been developed by insertion of lipidated protoporphyrin IX (PpIX lipid) into HVJ-E. In this study, we investigated the optimal conditions for PE preparation and laser irradiation for highly selective PDT using PE with a short drug-light interval. Materials and Methods: Human hormon refractory prostate cancer cell line PC-3 and human normal prostate epithelial cell line PNT2 were cultured. PpIX lipid uptake and cytotoxicity of PDT in the cells incubated with PE for 10 min were evaluated by measuring fluorescence intensity and by using a cell counting reagent 24 h after PDT, respectively. Results: PpIX lipid uptake and cytotoxicity of PDT were increased with PpIX lipid concentration. Cytotoxicity of PDT using PE was more than 9 times as strong as that with PpIX lipid and PpIX induced by 5-aminolevulinic acid. Much stronger cytotoxicity was induced in PC-3 cells than PNT2 cells with the ratio of cell death rate for cancer to normal cells up to 4.64 ± 0.09. Conclusions: Fast PS delivery with HVJ-E allows highly selective PDT with a short drug-light interval. Therefore, PDT using PE has a potential to shorten treatment period and reduce side effects of PDT.

Experimental study of red light therapy instrument combined with insulin on type 2 diabetic foot model rats

Objective: To investigate the therapeutic effect and clinical value of red light therapy combined with insulin therapy on wound in type 2 diabetic foot (DF) rats. Methords: Wistar rats were injected intraperitoneally with medium-dose high-fat and high-fat streptozotocin and carefully controlled at room temperature. The type 2 diabetes mellitus Wistar rats were reproved with high glucose and high fat streptozotocin (STZ) Foot involvement in the establishment of type 2 diabetic foot rat model. The rats were randomly divided into three groups: metformin 0.140 g/kg group, red light therapy group combined with insulin treatment group, model group, blank control group (30 d after intragastric administration of rats), further observation of each group of rat wounds Healing rate, insulin, blood glucose and blood lipid and vascular endothelial activity factors such as laboratory changes. Results: The observation of red light therapy combined with insulin treatment group was the most obvious, the difference was statistically significant, significantly promoted wound healing in DF rats, increased healing rate, increased insulin sensitivity (NO) and nitric oxide synthase (NOS) were increased in the serum of rats. The insulin resistance and platelet aggregation rate of the DF model rats were significantly higher than those of the control group, and the insulin sensitivity index (ISI) , Blood glucose, blood lipid, blood viscosity and endothelin (ET) and other active factors were significantly reduced. Conclusion: (1) treatment of red light therapy can improve blood rheology, improve glucose and lipid metabolism, improve insulin sensitivity, Vascular endothelial cell activation and so on to improve the wound healing rate of DF wound in rats. (2) The treatment of red light therapy is effective, safe and high in clinical application.

Zinc oxide nanoparticles with catalase-like nanozyme activity and near-infrared light response:A combination of effective photodynamic therapy,autophagy,ferroptosis,and antitumor immunity

We prepared biocompatible and environment-friendly zinc oxide nanoparticles(ZnO NPs)with upconversion properties and catalase-like nanozyme activity.Photodynamic therapy(PDT)application is severely limited by the poor penetration of UV-Visible light and a hypoxic tumor environment.Here,we used ZnO NPs as a carrier for the photosensitizer chlorin e6(Ce6)to construct zinc oxide-chlorin e6 nanoparticles(ZnO-Ce6 NPs),simultaneously addressing both problems.In terms of penetration,ZnO NPs convert 808 nm near-infrared light into 401 nm visible light to excite Ce6,achieving deep-penetrating photodynamic therapy under long-wavelength light.Interestingly,the ability to emit short-wavelength light under long-wavelength light is usually observed in upconversion nanoparticles.As nanozymes,ZnO NPs can catalyze the decomposition of hydrogen peroxide in tumors,providing oxygen for photodynamic action and relieving hypoxia.The enhanced photodynamic action produces a large amount of reactive oxygen species,which overactivate autophagy and trigger immunogenic cell death(ICD),leading to antitumor immunotherapy.In addition,even in the absence of light,ZnO and ZnO-Ce6 NPs can induce ferroptosis of tumor cells and exert antitumor effects.

Photodynamic Therapy with Phthalomethyl D: Perspectives against SARS-CoV-2

Background: Photodynamic therapy (PDT) is the generation of cytotoxic agents through the dynamic interaction between a photosensitizer excited by light at a specific wavelength. When associated with phthalocyanines, they are efficient in incorporating target cells and exhibiting high rates of triplet generation. This study aimed to characterize PDT associated with the phototherapeutic agent Phthalomethyl D, developed by the authors, in the process of repair, healing and immune improvement for possible application against SARS-CoV-2. Methods: Sixty-nine mice were used, divided into 2 groups: GI, treated with ILIB laser, without a phototherapeutic agent, and subjected to surgery for viral induction;GII, same as GI plus association of Phthalomethyl D. They were divided into subgroups and reevaluated at 7, 14, and 21 days, and then divided into 3 subgroups of 6 animals each, subjected to treatment at 24 h, 48 h, 72 h, 5 and 7 days. Results: Both groups had a high rate of partial incision closure and acute inflammatory control. Microscopically, there was a greater amount of amorphous fundamental substance, fibrocytes, fibroblasts, and giant cells and reduction in the number of keratinocytes, in the amount of keratin, and epidermal thickness in GII than in GI. Conclusions: PDT with Phthalomethyl D stimulates the processes of healing/repair and immunomodulation during viral infection, initially favoring the inflammatory response and, after 21 days, contributing to the anti-inflammatory response profile, making this approach possible in the treatment of individuals infected with SARS-CoV-2.

Effect of antibacterial photodynamic therapy on Streptococcus mutans plaque biofilm in vitro

The main objective of this study is to evaluate the antibacterial effect of antibacterial pho-todynamic therapy(aPDT)on Streptococcus mutans(S.mutans)biofilm model in vitro.The selection of photosensitizers is the key step for the efficacy of photodynamic therapy(PDT).However,no studies have been conducted in the oral field to compare the functional char-acteristics and application effects of PDT mediated by various photosensitizers.In this re-search,the antibacterial effect of Methylene blue(MB)/650 nm laser and Hematoporphyrin monomethyl ether(HMME)/532 nm laser on S.mutans biofilm was compared under different energy densities to provide experimental reference for the clinical application of the two PDT.The yield of lactic acid was analyzed by Colony forming unit(CFU)and spectrophotometry,and the complete biofilm activity was measured by Confocal Laser Scanning Microscopy(CLSM)to evaluate the bactericidal effect on each group.Based on the results of CFU,the bacterial colonies formed by 30.4J/cm^(2)532nm MB-aPDT group and 30.4J/cm^(2)532nm HMME-aPDT group were significantly less than those in other groups,and the bacterial colonies in HMME-aPDT group were less than those in HMME-aPDT group.Lactic acid production in all treatment groups except the photosensitizer group was statistically lower than that in the normal saline control group.The activity of bacterial plaque biofilm was significantly decreased in the two groups treated with 30.4 J/cm^(2) aPDT.Therefore,aPDT suitable for energy measurement can kill S.mutans plaque biofilm,and MB-aPDT is better than HMME-aPDT.

Evaluation of Self-Treatment of Acne Using Silk’n Blue Phototherapy System

Background: At-home phototherapy devices for the treatment of acne have emerged as an appealing treatment option and as an effective adjunct treatment to existing modalities. The principal goal of the study was to determine the changes in the number of inflammatory lesions in acne patients. Methods: Patients received instruction for daily at-home use of Silk’n Blue device for 12 weeks. Follow-up visits were conducted at 1 and 3 months to collect data. Results: Fifteen subjects with mild to severe cases experienced improvement over the course of the trial. The decrease in mean inflammatory acne counts (from 41.26 to 24.46) and mean percent reduction (41.8%) were statistically significant (p < 0.001). Some participants experienced percent reductions as great as 67%. No adverse events were recorded. Conclusions: The Silk’n Blue device is a safe and effective modality for at-home treatment of mild, moderate, and severe inflammatory acne vulgaris with proper use.

Study of Effects of Photodynamic Therapy(PDT),in Scar-Induced Skin Wounds in Rats Wistar:The New Clinical Perspective for Ulcers

Photodynamic therapy today is becoming an important role in the healing of lacerated tissues, since it has therapeutic resources capable of accelerating this process. One treatment option is the clinical phototherapy, and Photodynamic Therapy (PDT) is being widely used. This study aims to evaluate the effect of PDT on the healing of skin wounds in rats. We used a sample of 39 male rats Wistar divided into three groups, a control, a PDT-treated green and red with the last PDT. After 24 hours before the surgical incisions, PDT was used in both groups for 6 minutes and was evaluated in histological level, the inflammatory reaction and the repair process. The results showed that the granulation tissue was more developed in the irradiated group than in the control group and the amount of chronic inflammatory cells (monocytes, macrophages, lymphocytes and plasma cells) predominated with green phototherapy. The epithelialization in the wound margins and scarring with better quality occurred with red PDT (640 nm), which the higher deposition was of collagen. However, phototherapy not collimated of 640 nm (red) resulted in better anti-inflammatory effects. Given these answers with phototherapy not collimated green (525 nm) and red (640 nm), we conclude that the use of these wavelengths is possible with benefits, mainly with red LED.

PHOTOTHERAPY OF GINGIVITIS:PILOT CLINICAL STUDY

The goal of this work was to evaluate the safety and efficacy of the Red Light Emitted Toothbrush(R-LETB)emitting at wavelength of 663 nm with power density of 3.3mW/cm2 in combination with 0.1%-methylene blue(MB)solution for the reduction of plaque and treatment of gingivitis.A microbiological in vitro study and a pilot clinical study were conducted.The microbiological study has shown total suppression of pathogenicflora after a 3-min exposure to the dye solution followed by a 20-sec treatment with the R-LETB.For the clinical study,37 subjects of both sexes with gingivitis were enrolled and randomly assigned to one of two groups.Subjects in thefirst(treatment)group were instructed to rinse their mouth with MB solution provided for 1 min and then brush the teeth with the R-LETB and standardized toothpaste.The second(control)group used only the toothpaste and a regular toothbrush.Subjects in both groups followed their respective procedures 2 times a day(morning and evening)for 30 days.Indices of plaque,gingival bleeding,and inflammation were evaluated at 14-day and 30-day timepoints.In the both groups,all indices improved in comparison with baseline.However,the treatment group demonstrated more pronounced improvement of the studied indices that was attributed to additional anti-microbial action of red light and MB on gum tissue.Thus,the use of R-LETB with MB appears to have a multifactor therapeutic action on oral pathological microflora:mechanical removal of the bacteria and suppressing action on microorganisms due to photodynamic reaction.

Acute Tonsillopharyngitis: Photosensitizer Fluorescence-Guided in Topical Therapy

Background: As is observed in acute respiratory pandemics characterized by inflammation of the oropharynx, microbial transmission caused by viruses and bacteria through the upper respiratory tract can quickly affect the lower respiratory tract due to its ease of transmission, The challenges are presented in the development of an adequate lighting system to prevent infections of the upper respiratory treatment and highlight the importance of following the procedure due to fluorescence decay from the given light dose. Methods: for this purpose, our study evaluated the lighting distribution on the oropharynx established and determined under simulation by TracePro software. The photobleaching (PB) is obtained by different fluorescence analysis methods of photosensitizer (PS) in formulation located in the oropharynx and tonsils. A blue light emission system at 450 nm was studied to improve the distribution, uniformity, and ray’s incidence. The PB of the PS was investigated using two different methods for detecting fluorescence in the oropharynx by quantifying the active portion of the PS assessed by fluorescence spectroscopy for patients with pharyngotonsillitis by consuming 2.25 mg of curcumin in formulation after applying light by analysis of images in Software MatLab. Results: The lighting device showed a uniformity of 82% in the oropharynx. In healthy volunteers, the minimum energy of photodegradation of curcumin is 0.2 and the maximum energy is 17.4 J/cm2. We observed intensities of blue and green emission of the analyzed fluorescence images related to PS through fluorescence measurements. Conclusions: We conclude that the pharyngotonsillitis infections can be treated by using an adequate distribution of light in the oropharynx and by activating photosensitizing agents in the infection sites supported by the fluorescence of the compound.

The Case Report on the Effectiveness of Infrared Light on Acid Burn Victim

Burn injuries are common in Pakistan. However, most people are reluctant to have infrared treatment for their wounds. This study investigated the efficacy of infrared treatment on burn wounds. The procedure involved a burn victim who had sustained acid burns to the neck and face. Nectrotomy was done to remove dead tissue from the burn wound, and after treatment, Low-Level Light was used to reduce pain and enhance healing in the patient. Initial results showed mild hypertrophic scars, no stiffness. Post-operation therapy included physical training regimens and massage. The patient showed satisfactory results and felt less tightness in neck movements by the following treatment. The article concludes by showing that infrared light promoted repair and regrowth at a cellular level.

枇杷清痤方联合红蓝光交替照射治疗寻常型痤疮临床观察

目的探讨枇杷清痤方联合红蓝光交替照射治疗寻常型痤疮的效果及对皮肤屏障功能的影响。方法选取2021年1月—2023年1月山东省单县中医医院收治的寻常型痤疮患者82例,分为观察组与对照组,各41例。对照组予红蓝光交替照射,观察组在对照组基础上联合枇杷清痤方治疗,均持续治疗4周。观察两组患者临床疗效及治疗前后中医证候积分、皮肤屏障功能、皮肤油脂分泌程度变化。结果观察组患者治疗总有效率为92.68%(38/41),高于对照组的75.61%(31/41)(P<0.05)。治疗后,两组各中医证候积分均低于治疗前,且观察组均低于对照组(P<0.05);两组的皮肤经皮水丢量、pH值及皮肤油脂量亦均低于治疗前、角质层含水量高于治疗前,且观察组各指标改善情况均优于对照组(P<0.05)。结论枇杷清痤方联合红蓝光交替照射治疗寻常型痤疮,可加快患者皮肤屏障功能修护,提高临床效果。

Ce6 nanoassemblies:Molecular mechanism and strategies for combinational anticancer therapy Special Collection:Aggregation-Induced Processes and Functions

Nowadays,cancer has become the leading cause of death worldwide,driving the need for effective therapeutics to improve patient prognosis.Photodynamic therapy(PDT)has been widely applied as an antitumor modality,owing to its minimal invasiveness,localized tumor damage,and high safety profile.However,its efficacy is limited by poor stability of photosensitizers,inadequate tumor accumulation,and a complex tumor microenvironment.To overcome these challenges,extensive endeavors have been made to explore the co-assembly of the widely used photosensitizer chlorin e6(Ce6)with various functional small molecules to enhance pharmacodynamic activity.This review provides a comprehensive overview of current studies on Ce6-based nanoparticles for effective PDT and precise delivery of functional molecules.The self-assembly mechanism will be discussed in detail,with a focus on potential strategies for combinational therapy with PDT.