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14 pages, 21757 KiB

Open AccessFeature PaperArticle

Synthesis of Multifunctional Nanoparticles for the Combination of Photodynamic Therapy and Immunotherapy

by Mei-Hwa Lee, James L. Thomas, Jin-An Li, Jyun-Ren Chen, Tzong-Liu Wang and Hung-Yin Lin

Pharmaceuticals 2021, 14(6), 508; https://doi.org/10.3390/ph14060508 - 26 May 2021

Cited by 9 | Viewed by 3547

Abstract

Programmed death-ligand 1 protein (PD-L1) has been posited to have a major role in suppressing the immune system during pregnancy, tissue allografts, autoimmune disease and other diseases, such as hepatitis. Photodynamic therapy uses light and a photosensitizer to generate singlet oxygen, which causes [...] Read more.

Programmed death-ligand 1 protein (PD-L1) has been posited to have a major role in suppressing the immune system during pregnancy, tissue allografts, autoimmune disease and other diseases, such as hepatitis. Photodynamic therapy uses light and a photosensitizer to generate singlet oxygen, which causes cell death (phototoxicity). In this work, photosensitizers (such as merocyanine) were immobilized on the surface of magnetic nanoparticles. One peptide sequence from PD-L1 was used as the template and imprinted onto poly(ethylene-co-vinyl alcohol) to generate magnetic composite nanoparticles for the targeting of PD-L1 on tumor cells. These nanoparticles were characterized using dynamic light scattering, high-performance liquid chromatography, Brunauer-Emmett-Teller analysis and superconducting quantum interference magnetometry. Natural killer-92 cells were added to these composite nanoparticles, which were then incubated with human hepatoma (HepG2) cells and illuminated with visible light for various periods. The viability and apoptosis pathway of HepG2 were examined using a cell counting kit-8 and quantitative real-time polymerase chain reaction. Finally, treatment with composite nanoparticles and irradiation of light was performed using an animal xenograft model. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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11 pages, 3566 KiB

Open AccessArticle

A Skin Cancer Prophylaxis Study in Hairless Mice Using Methylene Blue, Riboflavin, and Methyl Aminolevulinate as Photosensitizing Agents in Photodynamic Therapy

by Hans Christian Wulf, Rami Nabil Al-Chaer, Martin Glud, Peter Alshede Philipsen and Catharina Margrethe Lerche

Pharmaceuticals 2021, 14(5), 433; https://doi.org/10.3390/ph14050433 - 5 May 2021

Cited by 9 | Viewed by 2956

Abstract

The high incidence of sunlight-induced human skin cancers reveals a need for more effective photosensitizing agents. In this study, we compared the efficacy of prophylactic photodynamic therapy (PDT) when methylene blue (MB), riboflavin (RF), or methyl aminolevulinate (MAL) were used as photosensitizers. All [...] Read more.

The high incidence of sunlight-induced human skin cancers reveals a need for more effective photosensitizing agents. In this study, we compared the efficacy of prophylactic photodynamic therapy (PDT) when methylene blue (MB), riboflavin (RF), or methyl aminolevulinate (MAL) were used as photosensitizers. All mice in four groups of female C3.Cg/TifBomTac hairless immunocompetent mice (N = 100) were irradiated with three standard erythema doses of solar-simulated ultraviolet radiation (UVR) thrice weekly. Three groups received 2 × 2 prophylactic PDT treatments (days 45 + 52 and 90 + 97). The PDT treatments consisted of topical administration of 16% MAL, 20% MB, or 20% RF, and subsequent illumination that matched the photosensitizers’ absorption spectra. Control mice received no PDT. We recorded when the first, second, and third skin tumors developed. The pattern of tumor development after MB-PDT or RF-PDT was similar to that observed in irradiated control mice (p > 0.05). However, the median times until the first, second, and third skin tumors developed in mice given MAL-PDT were significantly delayed, compared with control mice (256, 265, and 272 vs. 215, 222, and 230 days, respectively; p < 0.001). Only MAL-PDT was an effective prophylactic treatment against UVR-induced skin tumors in hairless mice. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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15 pages, 2665 KiB

Open AccessArticle

Study of Cytotoxic and Photodynamic Activities of Dyads Composed of a Zinc Phthalocyanine Appended to an Organotin

by Isabelle Toubia, Christophe Nguyen, Stéphane Diring, Marine Pays, Elodie Mattana, Philippe Arnoux, Céline Frochot, Magali Gary-Bobo, Marwan Kobeissi and Fabrice Odobel

Pharmaceuticals 2021, 14(5), 413; https://doi.org/10.3390/ph14050413 - 28 Apr 2021

Cited by 8 | Viewed by 3320

Abstract

The combination of photodynamic therapy and chemotherapy is a promising strategy to enhance cancer therapeutic efficacy and reduce drug resistance. In this study two zinc(II) phthalocyanine-tin(IV) conjugates linked by a triethylene glycol chain were synthesized and characterized. In these complexes, the zinc(II) phthalocyanine [...] Read more.

The combination of photodynamic therapy and chemotherapy is a promising strategy to enhance cancer therapeutic efficacy and reduce drug resistance. In this study two zinc(II) phthalocyanine-tin(IV) conjugates linked by a triethylene glycol chain were synthesized and characterized. In these complexes, the zinc(II) phthalocyanine was used as a potential photosensitizer for PDT and the tin complex was selected as cytostatic moiety. The two dyads composed of zinc(II) phthalocyanine and tin complexes exhibited high cytotoxicity, in absence of light stimulation, against MCF-7 human breast cancer cells with low LC₅₀ values in the range of 0.016–0.453 µM. In addition, these complexes showed superior cytotoxicity than their mixture of equimolar component, accompanied with a higher activity towards cancer cells compared to human healthy fibroblasts. However, under irradiation of the zinc phthalocyanine unit (at 650 nm) no photodynamic activity could be detected, due to the most likely quenching of zinc(II) phthalocyanine singlet excited state by the nearby tin complex according to a photoinduced electron transfer process. This study demonstrates the potential of heterometallic anticancer chemotherapeutics composed of a zinc phthalocyanine and tin complex, and it highlights that the development of such conjugates requires that the sensitizer preserves its photophysical properties and in particular its singlet oxygen sensitization ability in the conjugate in order to combine the PDT activity with the cytotoxicity of the anticancer drug. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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21 pages, 3281 KiB

Open AccessArticle

Terbium-Based AGuIX-Design Nanoparticle to Mediate X-ray-Induced Photodynamic Therapy

by Joël Daouk, Mathilde Iltis, Batoul Dhaini, Denise Béchet, Philippe Arnoux, Paul Rocchi, Alain Delconte, Benoît Habermeyer, François Lux, Céline Frochot, Olivier Tillement, Muriel Barberi-Heyob and Hervé Schohn

Pharmaceuticals 2021, 14(5), 396; https://doi.org/10.3390/ph14050396 - 22 Apr 2021

Cited by 6 | Viewed by 3279

Abstract

X-ray-induced photodynamic therapy is based on the energy transfer from a nanoscintillator to a photosensitizer molecule, whose activation leads to singlet oxygen and radical species generation, triggering cancer cells to cell death. Herein, we synthesized ultra-small nanoparticle chelated with Terbium (Tb) as a [...] Read more.

X-ray-induced photodynamic therapy is based on the energy transfer from a nanoscintillator to a photosensitizer molecule, whose activation leads to singlet oxygen and radical species generation, triggering cancer cells to cell death. Herein, we synthesized ultra-small nanoparticle chelated with Terbium (Tb) as a nanoscintillator and 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenyl porphyrin (P1) as a photosensitizer (AGuIX@Tb-P1). The synthesis was based on the AGuIX@ platform design. AGuIX@Tb-P1 was characterised for its photo-physical and physico-chemical properties. The effect of the nanoparticles was studied using human glioblastoma U-251 MG cells and was compared to treatment with AGuIX@ nanoparticles doped with Gadolinium (Gd) and P1 (AGuIX@Gd-P1). We demonstrated that the AGuIX@Tb-P1 design was consistent with X-ray photon energy transfer from Terbium to P1. Both nanoparticles had similar dark cytotoxicity and they were absorbed in a similar rate within the cells. Pre-treated cells exposure to X-rays was related to reactive species production. Using clonogenic assays, establishment of survival curves allowed discrimination of the impact of radiation treatment from X-ray-induced photodynamic effect. We showed that cell growth arrest was increased (35%-increase) when cells were treated with AGuIX@Tb-P1 compared to the nanoparticle doped with Gd. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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15 pages, 3031 KiB

Open AccessArticle

The Comparison of In Vitro Photosensitizing Efficacy of Curcumin-Loaded Liposomes Following Photodynamic Therapy on Melanoma MUG-Mel2, Squamous Cell Carcinoma SCC-25, and Normal Keratinocyte HaCaT Cells

by Marta Woźniak, Martyna Nowak, Anastasiia Lazebna, Kamil Więcek, Izabella Jabłońska, Krzysztof Szpadel, Aleksandra Grzeszczak, Jerzy Gubernator and Piotr Ziółkowski

Pharmaceuticals 2021, 14(4), 374; https://doi.org/10.3390/ph14040374 - 17 Apr 2021

Cited by 35 | Viewed by 3974

Abstract

The research focused on the investigation of curcumin encapsulated in hydrogenated soy phosphatidylcholine liposomes and its increased photoactive properties in photodynamic therapy (PDT). The goal of this study was two-fold: to emphasize the role of a natural photoactive plant-based derivative in the liposomal [...] Read more.

The research focused on the investigation of curcumin encapsulated in hydrogenated soy phosphatidylcholine liposomes and its increased photoactive properties in photodynamic therapy (PDT). The goal of this study was two-fold: to emphasize the role of a natural photoactive plant-based derivative in the liposomal formulation as an easily bioavailable, alternative photosensitizer (PS) for the use in PDT of skin malignancies. Furthermore, the goal includes to prove the decreased cytotoxicity of phototoxic agents loaded in liposomes toward normal skin cells. Research was conducted on melanoma (MugMel2), squamous cell carcinoma (SCC-25), and normal human keratinocytes (HaCaT) cell lines. The assessment of viability with MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) evaluated cell death after exposure to blue light irradiation after 4 h of pre-incubation with free and encapsulated curcumin. Additionally, the wound healing assay, flow cytometry, and immunocytochemistry to detect apoptosis were performed. The malignant cells revealed increased phototoxicity after the therapy in comparison to normal cells. Moreover, liposome curcumin-based photodynamic therapy showed an increased ratio of apoptotic and necrotic cells. The study also demonstrated that nanocurcumin significantly decreased malignant cell motility following PDT treatment. Acquired results suggest that liposomal formulation of a poor soluble natural compound may improve photosensitizing properties of curcumin-mediated PDT treatment in skin cancers and reduce toxicity in normal keratinocytes. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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19 pages, 5731 KiB

Open AccessArticle

Synergistic Photoantimicrobial Chemotherapy of Methylene Blue-Encapsulated Chitosan on Biofilm-Contaminated Titanium

by Chiu-Nan Lin, Shinn-Jyh Ding and Chun-Cheng Chen

Pharmaceuticals 2021, 14(4), 346; https://doi.org/10.3390/ph14040346 - 9 Apr 2021

Cited by 13 | Viewed by 2501

Abstract

Intensive efforts have been made to eliminate or substantial reduce bacterial adhesion and biofilm formation on titanium implants. However, in the management of peri-implantitis, the methylene blue (MB) photosensitizer commonly used in photoantimicrobial chemotherapy (PACT) is limited to a low retention on the [...] Read more.

Intensive efforts have been made to eliminate or substantial reduce bacterial adhesion and biofilm formation on titanium implants. However, in the management of peri-implantitis, the methylene blue (MB) photosensitizer commonly used in photoantimicrobial chemotherapy (PACT) is limited to a low retention on the implant surface. The purpose of this study was to assess enhancive effect of water-soluble quaternary ammonium chitosan (QTS) on MB retention on biofilm-infected SLA (sandblasted, large grid, and acid-etched) Ti alloy surfaces in vitro. The effectiveness of QTS + MB with different concentrations in eliminating Gram-negative A. actinomycetemcomitans or Gram-positive S. mutans bacteria was compared before and after PACT. Bacterial counting and lipopolysaccharide (LPS) detection were examined, and then the growth of human osteoblast-like MG63 cells was evaluated. The results indicated that the synergistic QTS + MB with retention ability significantly decreased the biofilm accumulation on the Ti alloy surface, which was better than the same concentration of 1 wt% methyl cellulose (MC). More importantly, the osteogenic activity of MG63 cells on the disinfected sample treated by QTS + MB-PACT modality was comparable to that of sterile Ti control, significantly higher than that by MC + MB-PACT modality. It is concluded that, in terms of improved retention efficacy, effective bacteria eradication, and enhanced cell growth, synergistically, PACT using the 100 μg/mL MB-encapsulated 1% QTS was a promising modality for the treatment of peri-implantitis. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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8 pages, 1059 KiB

Open AccessArticle

How Much Protoporphyrin IX Must Be Activated to Obtain Full Efficacy of Methyl Aminolevulinate Photodynamic Therapy? Implication for Treatment Modifications

by Hans Christian Wulf, Ida M. Heerfordt and Peter Alshede Philipsen

Pharmaceuticals 2021, 14(4), 333; https://doi.org/10.3390/ph14040333 - 6 Apr 2021

Cited by 8 | Viewed by 2475

Abstract

Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is a popular treatment for actinic keratoses (AK), and several PDT treatment modalities with similar cure rates are in use. The effect relies on the activation of protoporphyrin IX (PpIX) in premalignant cells. This study aimed [...] Read more.

Photodynamic therapy (PDT) with methyl aminolevulinate (MAL) is a popular treatment for actinic keratoses (AK), and several PDT treatment modalities with similar cure rates are in use. The effect relies on the activation of protoporphyrin IX (PpIX) in premalignant cells. This study aimed to measure PpIX during each treatment modality to determine the minimal PpIX activation and shortest exposure time for optimal cure rate. In four different treatment modalities, we established the PpIX formation up to three hours after MAL application without illumination and measured the speed of PpIX photoactivation during 9 min of red light (37 J/cm²). The level of PpIX three hours after MAL application was set to 100 PpIX units. In comparison, 85 PpIX units were formed during daylight PDT, 57 PpIX units during pulse PDT, and 52 PpIX units without any curettage prior to MAL. The activation of 50 PpIX units should, therefore, be enough to obtain a full effect on AK. Further, red light illumination may be shortened from 9 min to 1–2 min. The results indicate that PDT can be performed successfully with half the illumination time used in daylight PDT today and with one fourth of the illumination time used in classical PDT. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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21 pages, 4303 KiB

Open AccessEditor’s ChoiceArticle

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

by Bauyrzhan Myrzakhmetov, Philippe Arnoux, Serge Mordon, Samir Acherar, Irina Tsoy and Céline Frochot

Pharmaceuticals 2021, 14(2), 138; https://doi.org/10.3390/ph14020138 - 9 Feb 2021

Cited by 48 | Viewed by 5692

Abstract

Photodynamic therapy (PDT) is an innovative treatment of malignant or diseased tissues. The effectiveness of PDT depends on light dosimetry, oxygen availability, and properties of the photosensitizer (PS). Depending on the medium, photophysical properties of the PS can change leading to increase or [...] Read more.

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

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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11 pages, 3767 KiB

Open AccessArticle

Effectiveness of Riboflavin and Rose Bengal Photosensitizer Modified Adhesive Resin for Orthodontic Bonding

by Ali Alqerban

Pharmaceuticals 2021, 14(1), 48; https://doi.org/10.3390/ph14010048 - 10 Jan 2021

Cited by 22 | Viewed by 2971

Abstract

This study aimed to evaluate the effect of riboflavin (RF) and Rose Bengal (RB) photosensitizer modified adhesive resin on the degree of conversion (DC), and antimicrobial capacity after bonded to tooth surface. Different concentrations of RB and RF were prepared by homogenization method. [...] Read more.

This study aimed to evaluate the effect of riboflavin (RF) and Rose Bengal (RB) photosensitizer modified adhesive resin on the degree of conversion (DC), and antimicrobial capacity after bonded to tooth surface. Different concentrations of RB and RF were prepared by homogenization method. An ultraviolet light source A (UVA) (375 nm wavelength, 3 mW/cm² power) was used for 30 min irradiation. FTIR was performed for control and test adhesives to analyze the DC. Antibacterial testing was performed using the MTT assay. Metal brackets were bonded using the modified adhesives and subjected for SEM examination. The surfaces of teeth and metal brackets were examined at ×10 magnification for assessing adhesive remnant index (ARI) after PDT, 24 h and thermocycling. For DC, control group, 0.1% RB and RF after PDT showed the highest value. SEM imaging indicated lowest growth of Streptococcus mutans over 0.5% of RB-PDT and RF-PDT as compared to the control group. The MTT assay outcomes reported that the activity of S. mutans substantially decreased with the addition of a high amount of either RB or RF (p < 0.01). Mean ARI scores showed a significant difference between all groups. This study concluded that 0.1% of either RB or RF after PDT can be used for bonding orthodontic brackets to the tooth surface with substantial antibacterial properties. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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10 pages, 1562 KiB

Open AccessArticle

Antimicrobial Capacity and Surface Alterations Using Photodynamic Therapy and Light Activated Disinfection on Polymer-Infiltrated Ceramic Material Contaminated with Periodontal Bacteria

by Elzahraa Eldwakhly, Selma Saadaldin, Alhanoof Aldegheishem, Marwa Salah Mostafa and Mai Soliman

Pharmaceuticals 2020, 13(11), 350; https://doi.org/10.3390/ph13110350 - 29 Oct 2020

Cited by 4 | Viewed by 2940

Abstract

This study determined the antimicrobial efficiency of light-activated disinfection (LAD) and photodynamic therapy (PDT) on polymer-infiltrated ceramic network (PICN) material contaminated with three periodontal bacteria and explored if PDT and LAD cause PICN surface alterations. Sixty PICN discs were contaminated with Tannerella forsythia [...] Read more.

This study determined the antimicrobial efficiency of light-activated disinfection (LAD) and photodynamic therapy (PDT) on polymer-infiltrated ceramic network (PICN) material contaminated with three periodontal bacteria and explored if PDT and LAD cause PICN surface alterations. Sixty PICN discs were contaminated with Tannerella forsythia, Porphyromonas gingivalis, and Treponema denticola and randomly divided into five groups (n = 12 samples/each) according to the treatment groups: Group PDT—PDT (630 ± 10 nm diode laser) with methylene blue; Group DL—808 nm diode laser in contact mode without photosensitizer; Group MB–methylene blue without light application; Group CHX—0.12% chlorhexidine digluconate solution and; Group NT—no treatment. Each disc was then placed in tubes containing phosphate buffered saline (PBS) and vortexed for 30 s to remove the remaining bacteria from the discs. A total of 10× serial dilutions were performed followed by plating of 30 μL of suspension on Brucella agar plates. The colony forming units (CFU) were calculated after 72 h. PICN discs with the attached biofilms were used for confocal microscopy investigation for live/dead bacterial viability. A random single sample from each group was selected to study the bacterial adherence and topographical alterations on PICN discs under scanning electron microscope (SEM). The PDT group showed higher reduction for each bacterial species and total counts of bacteria assessed followed by the DL group (p < 0.05). When compared with MB group, the two laser groups were significantly superior (p < 0.05). The MB group did not show significant differences for any bacteria when compared to NT. The bacteria with the CHX group and DL groups appeared dead with few areas of surviving green stained bacteria. The PDT group showed the highest dead cell count (p < 0.05). PDT and DL groups indicate no significant changes on the surface compared to the sterile PICN discs on visual assessment. Photodynamic therapy produced superior periodontal bacteria reduction over the surface of PICN surface. PDT group showed higher reduction for each bacterial species and total counts of bacteria assessed followed by the DL group. Both PDT and DL treatment strategies are effective without producing surface alterations on PICN. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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10 pages, 2537 KiB

Open AccessArticle

Novel Photosensitizer β-Mannose-Conjugated Chlorin e6 as a Potent Anticancer Agent for Human Glioblastoma U251 Cells

by Yo Shinoda, Kohei Kujirai, Kohei Aoki, Mai Morita, Masato Masuda, Lihao Zhang, Zhou Kaixin, Akihiro Nomoto, Tsutomu Takahashi, Yayoi Tsuneoka, Jiro Akimoto, Hiromi Kataoka, Rioko Rachi, Atsushi Narumi, Tomokazu Yoshimura, Shigenobu Yano and Yasuyuki Fujiwara

Pharmaceuticals 2020, 13(10), 316; https://doi.org/10.3390/ph13100316 - 16 Oct 2020

Cited by 13 | Viewed by 3967

Abstract

A photosensitizer is a molecular drug for photodynamic diagnosis and photodynamic therapy (PDT) against cancer. Many studies have developed photosensitizers, but improvements in their cost, efficacy, and side effects are needed for better PDT of patients. In the present study, we developed a [...] Read more.

A photosensitizer is a molecular drug for photodynamic diagnosis and photodynamic therapy (PDT) against cancer. Many studies have developed photosensitizers, but improvements in their cost, efficacy, and side effects are needed for better PDT of patients. In the present study, we developed a novel photosensitizer β-mannose-conjugated chlorin e6 (β-M-Ce6) and investigated its PDT effects in human glioblastoma U251 cells. U251 cells were incubated with β-M-Ce6, followed by laser irradiation. Cell viability was determined using the Cell Counting Kit-8 assay. The PDT effects of β-M-Ce6 were compared with those of talaporfin sodium (TS) and our previously reported photosensitizer β-glucose-conjugated chlorin e6 (β-G-Ce6). Cellular uptake of each photosensitizer and subcellular distribution were analyzed by fluorescence microscopy. β-M-Ce6 showed 1000× more potent PDT effects than those of TS, and these were similar to those of β-G-Ce6. β-M-Ce6 accumulation in U251 cells was much faster than TS accumulation and distributed to several organelles such as the Golgi apparatus, mitochondria, and lysosomes. This rapid cellular uptake was inhibited by low temperature, which suggested that β-M-Ce6 uptake uses biological machinery. β-M-Ce6 showed potent PDT anti-cancer effects compared with clinically approved TS, which is a possible candidate as a next generation photosensitizer in cancer therapy. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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Review

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21 pages, 653 KiB

Open AccessReview

Photodynamic Therapy Combined with Antibiotics or Antifungals against Microorganisms That Cause Skin and Soft Tissue Infections: A Planktonic and Biofilm Approach to Overcome Resistances

by Vanesa Pérez-Laguna, Isabel García-Luque, Sofía Ballesta, Antonio Rezusta and Yolanda Gilaberte

Pharmaceuticals 2021, 14(7), 603; https://doi.org/10.3390/ph14070603 - 23 Jun 2021

Cited by 25 | Viewed by 3556

Abstract

The present review covers combination approaches of antimicrobial photodynamic therapy (aPDT) plus antibiotics or antifungals to attack bacteria and fungi in vitro (both planktonic and biofilm forms) focused on those microorganisms that cause infections in skin and soft tissues. The combination can prevent [...] Read more.

The present review covers combination approaches of antimicrobial photodynamic therapy (aPDT) plus antibiotics or antifungals to attack bacteria and fungi in vitro (both planktonic and biofilm forms) focused on those microorganisms that cause infections in skin and soft tissues. The combination can prevent failure in the fight against these microorganisms: antimicrobial drugs can increase the susceptibility of microorganisms to aPDT and prevent the possibility of regrowth of those that were not inactivated during the irradiation; meanwhile, aPDT is effective regardless of the resistance pattern of the strain and their use does not contribute to the selection of antimicrobial resistance. Additive or synergistic antimicrobial effects in vitro are evaluated and the best combinations are presented. The use of combined treatment of aPDT with antimicrobials could help overcome the difficulty of fighting high level of resistance microorganisms and, as it is a multi-target approach, it could make the selection of resistant microorganisms more difficult. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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29 pages, 1680 KiB

Open AccessFeature PaperEditor’s ChoiceReview

Current Prospects for Treatment of Solid Tumors via Photodynamic, Photothermal, or Ionizing Radiation Therapies Combined with Immune Checkpoint Inhibition (A Review)

by Sanjay Anand, Timothy A. Chan, Tayyaba Hasan and Edward V. Maytin

Pharmaceuticals 2021, 14(5), 447; https://doi.org/10.3390/ph14050447 - 10 May 2021

Cited by 35 | Viewed by 4317

Abstract

Photodynamic therapy (PDT) causes selective damage to tumor cells and vasculature and also triggers an anti-tumor immune response. The latter fact has prompted the exploration of PDT as an immune-stimulatory adjuvant. PDT is not the only cancer treatment that relies on electromagnetic energy [...] Read more.

Photodynamic therapy (PDT) causes selective damage to tumor cells and vasculature and also triggers an anti-tumor immune response. The latter fact has prompted the exploration of PDT as an immune-stimulatory adjuvant. PDT is not the only cancer treatment that relies on electromagnetic energy to destroy cancer tissue. Ionizing radiation therapy (RT) and photothermal therapy (PTT) are two other treatment modalities that employ photons (with wavelengths either shorter or longer than PDT, respectively) and also cause tissue damage and immunomodulation. Research on the three modalities has occurred in different “silos”, with minimal interaction between the three topics. This is happening at a time when immune checkpoint inhibition (ICI), another focus of intense research and clinical development, has opened exciting possibilities for combining PDT, PTT, or RT with ICI to achieve improved therapeutic benefits. In this review, we surveyed the literature for studies that describe changes in anti-tumor immunity following the administration of PDT, PTT, and RT, including efforts to combine each modality with ICI. This information, collected all in one place, may make it easier to recognize similarities and differences and help to identify new mechanistic hypotheses toward the goal of achieving optimized combinations and tumor cures. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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13 pages, 908 KiB

Open AccessReview

Systematic Review and Meta-Analysis of In Vitro Anti-Human Cancer Experiments Investigating the Use of 5-Aminolevulinic Acid (5-ALA) for Photodynamic Therapy

by Yo Shinoda, Daitetsu Kato, Ryosuke Ando, Hikaru Endo, Tsutomu Takahashi, Yayoi Tsuneoka and Yasuyuki Fujiwara

Pharmaceuticals 2021, 14(3), 229; https://doi.org/10.3390/ph14030229 - 7 Mar 2021

Cited by 23 | Viewed by 4174

Abstract

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. [...] Read more.

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2021)

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