Research

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14 pages, 1400 KiB

Open AccessArticle

Residual Microscopic Peritoneal Metastases after Macroscopic Complete Cytoreductive Surgery for Advanced High-Grade Serous Ovarian Carcinoma: A Target for Folate Receptor Targeted Photodynamic Therapy?

by Morgane Moinard, Jeremy Augustin, Marine Carrier, Elisabeth Da Maïa, Alix Penel, Jérémie Belghiti, Maryam Nikpayam, Clémentine Gonthier, Geoffroy Canlorbe, Samir Acherar, Nadira Delhem, Céline Frochot, Catherine Uzan and Henri Azaïs

Pharmaceuticals 2022, 15(8), 1034; https://doi.org/10.3390/ph15081034 - 22 Aug 2022

Cited by 2 | Viewed by 1993

Abstract

Despite conventional treatment combining complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy, residual microscopic peritoneal metastases (mPM) may persist as the cause of peritoneal recurrence in 60% of patients. Therefore, there is a real need to specifically target these mPM to definitively eradicate [...] Read more.

Despite conventional treatment combining complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy, residual microscopic peritoneal metastases (mPM) may persist as the cause of peritoneal recurrence in 60% of patients. Therefore, there is a real need to specifically target these mPM to definitively eradicate any traces of the disease and improve patient survival. Therapeutic targeting method, such as photodynamic therapy, would be a promising method for such a purpose. Folate receptor alpha (FRα), as it is specifically overexpressed by cancer cells from various origins, including ovarian cancer cells, is a good target to address photosensitizing molecules. The aim of this study was to determine FRα expression by residual mPM after complete macroscopic CRS in patients with advanced high-grade serous ovarian cancer (HGSOC). A prospective study conducted between 1 June 2018 and 10 July 2019 in a single referent center accredited by the European Society of Gynecological Oncology for advanced EOC surgical management. Consecutive patients presenting with advanced HGSOC and eligible for complete macroscopic CRS were included. Up to 13 peritoneal biopsies were taken from macroscopically healthy peritoneum at the end of CRS and examined for the presence of mPM. In case of detection of mPM, a systematic search for RFα expression by immunohistochemistry was performed. Twenty-six patients were included and 26.9% presented mPM. In the subgroup of patients with mPM, FRα expression was positive on diagnostic biopsy before neoadjuvant chemotherapy for 67% of patients, on macroscopic peritoneal metastases for 86% of patients, and on mPM for 75% of patients. In the subgroup of patients with no mPM, FRα expression was found on diagnostic biopsy before neoadjuvant chemotherapy in 29% of patients and on macroscopic peritoneal metastases in 78% of patients. FRα is well expressed by patients with or without mPM after complete macroscopic CRS in patients with advanced HGSOC. In addition to conventional cytoreductive surgery, the use of a therapeutic targeting method, such as photodynamic therapy, by addressing photosensitizing molecules that specifically target FRα may be studied. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2022)

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12 pages, 2711 KiB

Open AccessArticle

Increased PDT Efficacy When Associated with Nitroglycerin: A Study on Retinoblastoma Xenografted on Mice

by Carole D. Thomas, Mihaela Lupu, Florent Poyer, Philippe Maillard and Joël Mispelter

Pharmaceuticals 2022, 15(8), 985; https://doi.org/10.3390/ph15080985 - 10 Aug 2022

Cited by 2 | Viewed by 1500

Abstract

Purposes: The aim of the study was to assess the efficacy of a treatment protocol that combines photodynamic therapy (PDT) and nitroglycerin (NG) on human retinoblastoma tumors xenografted on mice. We aimed to increase the PDT efficiency (in our least treatment-responsive retinoblastoma line) [...] Read more.

Purposes: The aim of the study was to assess the efficacy of a treatment protocol that combines photodynamic therapy (PDT) and nitroglycerin (NG) on human retinoblastoma tumors xenografted on mice. We aimed to increase the PDT efficiency (in our least treatment-responsive retinoblastoma line) with better PS delivery to the tumor generated by NG, which is known to dilate vessels and enhance the permeability and retention of macromolecules in solid tumors. Methods: In vivo follow-up of the therapeutic effects was performed by sodium MRI, which directly monitors variations in sodium concentrations non-invasively and can be used to track the tumor response to therapy. NG ointment was applied one hour before PDT. The PDT protocol involves double-tumor targeting, i.e., cellular and vascular. The first PS dose was injected followed by a second one, separated by a 3 h interval. The timelapse allowed the PS molecules to penetrate tumor cells. Ten minutes after the second dose, the PS was red-light-activated. Results: In this study, we observed that the PDT effect was enhanced by applying nitroglycerin ointment to the tumor-bearing animal’s skin. PDT initiates the bystander effect on retinoblastomas, and NG increases this effect by increasing the intratumoral concentration of PS, which induces a higher production of ROS in the illuminated region and thus increases the propagation of the cell death signal deeper into the tumor (bystander effect). Full article

(This article belongs to the Special Issue Photodynamic Therapy 2022)

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8 pages, 506 KiB

Open AccessEditor’s ChoiceArticle

Clinical Efficacy and Safety of Antimicrobial Photodynamic Therapy in Residual Periodontal Pockets during the Maintenance Phase

by Yasunori Yamashita, Megumi Mae, Masayuki Oohira, Yukio Ozaki, Seigo Ohba, Izumi Asahina and Atsutoshi Yoshimura

Pharmaceuticals 2022, 15(8), 924; https://doi.org/10.3390/ph15080924 - 25 Jul 2022

Cited by 5 | Viewed by 1589

Abstract

Antimicrobial photodynamic therapy (a-PDT) in combination with scaling root planing (SRP) is more effective at improving periodontal status than SRP alone. However, the effectiveness of a-PDT in combination with irrigation for patients undergoing periodontal maintenance has not been clarified. This study evaluated the [...] Read more.

Antimicrobial photodynamic therapy (a-PDT) in combination with scaling root planing (SRP) is more effective at improving periodontal status than SRP alone. However, the effectiveness of a-PDT in combination with irrigation for patients undergoing periodontal maintenance has not been clarified. This study evaluated the efficacy and safety of a-PDT in the maintenance phase. Patients who had multiple sites with bleeding on probing (BOP) and periodontal probing depth (PPD) of 4–6 mm in the maintenance phase were treated with a split-mouth design. These sites were randomly assigned to one of two groups: the a-PDT group and the irrigation group. In the a-PDT group, the periodontal pockets were treated with light-sensitive toluidine blue and a light irradiator. In the irrigation group, the periodontal pockets were simply irrigated using an ultrasonic scaler. After 7 days, the safety and efficacy of a-PDT were assessed. The mean PPD of the a-PDT group had reduced from 4.50 mm to 4.13 mm, whereas negligible change was observed in the irrigation group. BOP significantly improved from 100% to 33% in the PDT group, whereas it hardly changed in the irrigation group. No adverse events were observed in any patients. a-PDT may be useful as a noninvasive treatment in the maintenance phase, especially in patients with relatively deep periodontal pocket. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2022)

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7 pages, 607 KiB

Open AccessArticle

Combination of Photodynamic Therapy and Oral Antifungals for the Treatment of Onychomycosis

by Alba Navarro-Bielsa, Tamara Gracia-Cazaña, Pilar Robres, Concepción Lopez, María Dolores Calvo-Priego, Carmen Aspiroz and Yolanda Gilaberte

Pharmaceuticals 2022, 15(6), 722; https://doi.org/10.3390/ph15060722 - 07 Jun 2022

Cited by 5 | Viewed by 2123

Abstract

Onychomycosis accounts for 50% of nail disorders, making it one of the most prevalent fungal diseases and a therapeutic challenge. Photodynamic therapy (PDT) could constitute a therapeutic alternative, owing to its good adherence, the low probability of resistance, the lack of interaction with [...] Read more.

Onychomycosis accounts for 50% of nail disorders, making it one of the most prevalent fungal diseases and a therapeutic challenge. Photodynamic therapy (PDT) could constitute a therapeutic alternative, owing to its good adherence, the low probability of resistance, the lack of interaction with antimicrobials, and its favorable adverse effect profile. This retrospective observational study included all patients with a microbiological diagnosis of onychomycosis treated with PDT at Miguel Servet University Hospital, Zaragoza (Spain), between January 2013 and June 2021. The protocol consisted of pre-treatment with 40% urea for 7 days, followed by 16% methyl-aminolevulinate (MAL) for 3 h and subsequent irradiation with a red-light LED lamp (37 J/cm²), every 1 or 2 weeks. Combined treatment with oral and/or topical antifungals was recorded. Of the 20 patients included (mean age, 59 ± 17 years), 55% were men. The most frequently detected microorganism was Trichophyton rubrum (55%). The most commonly affected location was the feet (90%): 50% of these cases were associated with tinea pedis. The median (standard deviation) number of PDT sessions was 6 (2.8). PDT was combined with systemic terbinafine (250 mg/day) in 10 cases (in 8 cases, this was administered for only 1 month), and with topical terbinafine in 3 cases. A complete clinical response was achieved in 80% (16) of cases and microbiological cure in 60% (12). PDT is a therapeutic alternative for onychomycosis, and can be administered either in monotherapy or combined with antifungals, allowing for a reduction in the duration and possible adverse effects of antifungal treatment and achieving higher cure rates than those obtained with either treatment alone. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2022)

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16 pages, 4065 KiB

Open AccessArticle

Cathepsin B-Cleavable Polymeric Photosensitizer Prodrug for Selective Photodynamic Therapy: In Vitro Studies

by Manish Jain, Jordan Bouilloux, Ines Borrego, Stéphane Cook, Hubert van den Bergh, Norbert Lange, Georges Wagnieres and Marie-Noelle Giraud

Pharmaceuticals 2022, 15(5), 564; https://doi.org/10.3390/ph15050564 - 30 Apr 2022

Cited by 10 | Viewed by 2344

Abstract

Cathepsin B is a lysosomal cysteine protease that plays an important role in cancer, atherosclerosis, and other inflammatory diseases. The suppression of cathepsin B can inhibit tumor growth. The overexpression of cathepsin B can be used for the imaging and photodynamic therapy (PDT) [...] Read more.

Cathepsin B is a lysosomal cysteine protease that plays an important role in cancer, atherosclerosis, and other inflammatory diseases. The suppression of cathepsin B can inhibit tumor growth. The overexpression of cathepsin B can be used for the imaging and photodynamic therapy (PDT) of cancer. PDT targeting of cathepsin B may have a significant potential for selective destruction of cells with high cathepsin B activity. We synthesized a cathepsin B-cleavable polymeric photosensitizer prodrug (CTSB-PPP) that releases pheophorbide a (Pha), an efficient photosensitizer upon activation with cathepsin B. We determined the concentration dependant uptake in vitro, the safety, and subsequent PDT-induced toxicity of CTSB-PPP, and ROS production. CTSB-PPP was cleaved in bone marrow cells (BMCs), which express a high cathepsin B level. We showed that the intracellular fluorescence of Pha increased with increasing doses (3–48 µM) and exerted significant dark toxicity above 12 µM, as assessed by MTT assay. However, 6 µM showed no toxicity on cell viability and ex vivo vascular function. Time-dependent studies revealed that cellular accumulation of CTSB-PPP (6 µM) peaked at 60 min of treatment. PDT (light dose: 0–100 J/cm², fluence rate: 100 mW/cm²) was applied after CTSB-PPP treatment (6 µM for 60 min) using a special frontal light diffuser coupled to a diode laser (671 nm). PDT resulted in a light dose-dependent reduction in the viability of BMCs and was associated with an increased intracellular ROS generation. Fluorescence and ROS generation was significantly reduced when the BMCs were pre-treated with E64-d, a cysteine protease inhibitor. In conclusion, we provide evidence that CTSB-PPP showed no dark toxicity at low concentrations. This probe could be utilized as a potential imaging agent to identify cells or tissues with cathepsin B activity. CTSB-PPP-based PDT results in effective cytotoxicity and thus, holds great promise as a therapeutic agent for achieving the selective destruction of cells with high cathepsin B activity. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2022)

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14 pages, 2037 KiB

Open AccessArticle

Synergistic Effect of Combination of a Temoporfin-Based Photodynamic Therapy with Potassium Iodide or Antibacterial Agents on Oral Disease Pathogens In Vitro

by Yin-Hwa Shih, Cheng-Chia Yu, Kai-Chi Chang, Yu-Hsin Tseng, Po-Jung Li, Shih-Min Hsia, Kuo-Chou Chiu and Tzong-Ming Shieh

Pharmaceuticals 2022, 15(4), 488; https://doi.org/10.3390/ph15040488 - 18 Apr 2022

Cited by 4 | Viewed by 2122

Abstract

5, 10, 15, 20-Tetrakis(3-hydroxyphenyl)chlorin (temoporfin) is a photosensitizer used in photodynamic therapy for oral cancer and periodontal disease treatment. This study determined the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of temoporfin. Additionally, the combination of potassium iodide (KI) or antimicrobial [...] Read more.

5, 10, 15, 20-Tetrakis(3-hydroxyphenyl)chlorin (temoporfin) is a photosensitizer used in photodynamic therapy for oral cancer and periodontal disease treatment. This study determined the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of temoporfin. Additionally, the combination of potassium iodide (KI) or antimicrobial agents in oral pathogens under hypoxic or normoxic conditions were determined. We also evaluated the biofilm removal effect and detected the expressions of the antibiotic resistance-related genes and biofilm formation-related genes of methicillin-resistant staphylococcus aureus (MRSA). The results provided reveal that the combination of the temoporfin and KI had a synergistic effect of reducing the MICs and MBCs of Lactobacillus acidophilus and Lactobacillus paracasei under normoxic and hypoxic conditions due to increasing H₂O₂ production. Temoporfin increased the biofilm removal of Aggregatibacter actinomycetemcomitans, Enterococcus faecalis, and Staphylococcus aureus under normoxic condition, and it reduced the antibiotic resistance-related genes expression of MRSA. The combination of temoporfin with ampicillin or chlorhexidine significantly enhanced the bactericidal effect on MRSA. This study provides a potential application of temoporfin on the clinical side against oral pathogens and the prevention of oral diseases. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2022)

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Review

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15 pages, 667 KiB

Open AccessReview

Photodynamic Therapy: A Prospective Therapeutic Approach for Viral Infections and Induced Neoplasia

by Ivan S. Mfouo-Tynga and Augustin G. Mouinga-Ondeme

Pharmaceuticals 2022, 15(10), 1273; https://doi.org/10.3390/ph15101273 - 16 Oct 2022

Cited by 3 | Viewed by 1459

Abstract

The recent COVID-19 pandemic outbreak and arising complications during treatments have highlighted and demonstrated again the evolving ability of microorganisms, especially viral resistance to treatment as they develop into new and strong strains. The search for novel and effective treatments to counter the [...] Read more.

The recent COVID-19 pandemic outbreak and arising complications during treatments have highlighted and demonstrated again the evolving ability of microorganisms, especially viral resistance to treatment as they develop into new and strong strains. The search for novel and effective treatments to counter the effects of ever-changing viruses is undergoing. Although it is an approved procedure for treating cancer, photodynamic therapy (PDT) was first used against bacteria and has now shown potential against viruses and certain induced diseases. PDT is a multi-stage process and uses photosensitizing molecules (PSs) that accumulate in diseased tissues and eradicates them after being light-activated in the presence of oxygen. In this review, studies describing viruses and their roles in disrupting cell regulation mechanisms and signaling pathways and facilitating tumorigenesis were described. With the development of innovative “or smart” PSs through the use of nanoparticles and two-photon excitation, among other strategies, PDT can boost immune responses, inactivate viral infections, and eradicate neoplastic cells. Visualization and monitoring of biological processes can be achieved in real-time with nanomedicines and better tissue penetration strategies. After photodynamic inactivation of viruses, signaling pathways seem to be restored but the underlying mechanisms are still to be elucidated. Light-mediated treatments are suitable to manage both oncogenic viral infections and induced neoplasia. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2022)

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54 pages, 15050 KiB

Open AccessReview

Importance of Rose Bengal Loaded with Nanoparticles for Anti-Cancer Photodynamic Therapy

by Batoul Dhaini, Laurène Wagner, Morgane Moinard, Joël Daouk, Philippe Arnoux, Hervé Schohn, Perrine Schneller, Samir Acherar, Tayssir Hamieh and Céline Frochot

Pharmaceuticals 2022, 15(9), 1093; https://doi.org/10.3390/ph15091093 - 31 Aug 2022

Cited by 11 | Viewed by 4214

Abstract

Rose Bengal (RB) is a photosensitizer (PS) used in anti-cancer and anti-bacterial photodynamic therapy (PDT). The specific excitation of this PS allows the production of singlet oxygen and oxygen reactive species that kill bacteria and tumor cells. In this review, we summarize the [...] Read more.

Rose Bengal (RB) is a photosensitizer (PS) used in anti-cancer and anti-bacterial photodynamic therapy (PDT). The specific excitation of this PS allows the production of singlet oxygen and oxygen reactive species that kill bacteria and tumor cells. In this review, we summarize the history of the use of RB as a PS coupled by chemical or physical means to nanoparticles (NPs). The studies are divided into PDT and PDT excited by X-rays (X-PDT), and subdivided on the basis of NP type. On the basis of the papers examined, it can be noted that RB used as a PS shows remarkable cytotoxicity under the effect of light, and RB loaded onto NPs is an excellent candidate for nanomedical applications in PDT and X-PDT. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2022)

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19 pages, 1670 KiB

Open AccessReview

Aspects of Antiviral Strategies Based on Different Phototherapy Approaches: Hit by the Light

by Hannah Kunstek, Fanny Vreken, Aminata Keita, Michael R. Hamblin, Florence Dumarçay and Mihayl Varbanov

Pharmaceuticals 2022, 15(7), 858; https://doi.org/10.3390/ph15070858 - 13 Jul 2022

Cited by 5 | Viewed by 3013

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which caused the COVID-19 pandemic spreading around the world from late 2019, served as a ruthless reminder of the threat viruses pose to global public health. The synthesis of new antiviral drugs, as well as [...] Read more.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which caused the COVID-19 pandemic spreading around the world from late 2019, served as a ruthless reminder of the threat viruses pose to global public health. The synthesis of new antiviral drugs, as well as repurposing existing products, is a long-term ongoing process which has challenged the scientific community. One solution could be an effective, accessible, and rapidly available antiviral treatment based on phototherapy (PT). PT has been used to treat several diseases, and relies on the absorption of light by endogenous molecules or exogenous photosensitizers (PS). PT has often been used in cancer treatment and prophylaxis, and as a complement to established chemotherapy and immunotherapy in combined therapeutic strategy. Besides significant applications in anticancer treatment, studies have demonstrated the beneficial impact of PT on respiratory, systemic, emerging, and oncogenic viral infections. The aim of this review was to highlight the potential of PT to combat viral infections by summarizing current progress in photodynamic, photothermal, and photoacoustic approaches. Attention is drawn to the virucidal effect of PT on systemic viruses such as the human immunodeficiency virus and human herpes viruses, including the causative agent of Kaposi sarcoma, human herpes virus (HHV8). PT has good potential for disinfection in anti-norovirus research and against pandemic viruses like SARS-CoV-2. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2022)

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11 pages, 529 KiB

Open AccessReview

The Potential Application of Natural Photosensitizers Used in Antimicrobial Photodynamic Therapy against Oral Infections

by Shima Afrasiabi, Alireza Partoazar, Nasim Chiniforush and Ramin Goudarzi

Pharmaceuticals 2022, 15(6), 767; https://doi.org/10.3390/ph15060767 - 20 Jun 2022

Cited by 16 | Viewed by 3072

Abstract

Oral health problems and the emergence of antimicrobial resistance among pathogenic bacterial strains have become major global challenges and are essential elements that negatively affect general well-being. Antimicrobial photodynamic therapy (APDT) is based on a light source and oxygen that activates a nontoxic [...] Read more.

Oral health problems and the emergence of antimicrobial resistance among pathogenic bacterial strains have become major global challenges and are essential elements that negatively affect general well-being. Antimicrobial photodynamic therapy (APDT) is based on a light source and oxygen that activates a nontoxic photosensitizer, resulting in microbial destruction. Synthetic and natural products can be used to help the APDT against oral microorganisms. The undesirable consequences of conventional photosensitizers, including toxicity, and cost encourage researchers to explore new promising photosensitizers based on natural compounds such as curcumin, chlorella, chlorophyllin, phycocyanin, 5-aminolevulinic acid, and riboflavin. In this review, we summarize in vitro studies describing the potential use of APDT therapy conjugated with some natural products against selected microorganisms that are considered to be responsible for oral infections. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2022)

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