Photodynamic Therapy

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Topic Information

Dear Colleagues,

Dedicating a volume to photodynamic therapy takes on great significance since it means that many steps have been taken to understand that such therapy can take on meaning. In 1903, Von Tappeiner, Director of the Pharmacology Department of the University of Munich, in collaboration with his student, Oscar Raab, demonstrated the therapeutic action of light combined with a photosensitizer and oxygen and coined the term "photodynamic action". Since that time, many studies have experimentally verified the veracity of the effectiveness on different biological structures. In medicine, the use of photodynamic therapy (PDT) is now widely documented and well codified for the treatment of oncological and non-oncological diseases such as macular degeneration of the retina and carcinoma of the esophagus and lung. In dermatology, the use varies from oncological diseases such as basal cell carcinoma, squamous cell carcinoma, actinic and non-oncological keratoses, bacterial, fungal, viral, immunological or inflammatory infections in the treatment of chronic wounds, and, finally, in cosmetology for the photo rejuvenation. PDT is based on the cytotoxic action of some hyperactive oxygen species, especially singlet oxygen but also superoxide anion and hydroxyl radicals, generated by the transfer of energy and/or electrons from the photoexcited oxygen sensitizer. Three important mechanisms are responsible for the efficacy of PDT: (1) direct death of tumor cells or inflammation, (2) damage to tumor vessels, (3) immunological response associated with the stimulation of leukocytes and the release of interleukins and other cytokines, growth factors, complement components, acute phase proteins and other immunoregulators. This topic aims to cover all aspects of photodynamic therapy including the discovery of new natural and synthetic photosensitizers, biomaterials and nanotechnology, in vitro and in vivo studies and clinical trials. With the collaboration of all of us, this volume will strengthen and stimulate further research!

Dr. Stefano Bacci
Prof. Dr. Kyungsu Kang
Topic Editors

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5 pages, 214 KiB  

Open AccessEditorial

Photodynamic Therapy

by Kyungsu Kang and Stefano Bacci

Biomedicines 2022, 10(11), 2701; https://doi.org/10.3390/biomedicines10112701 - 26 Oct 2022

Cited by 6 | Viewed by 1596

Abstract

In 1903, Von Tappeiner and Jesionek [...] Full article

(This article belongs to the Topic Photodynamic Therapy)

16 pages, 1141 KiB  

Open AccessReview

Near-Infrared Photoimmunotherapy for Thoracic Cancers: A Translational Perspective

by Kohei Matsuoka, Mizuki Yamada, Mitsuo Sato and Kazuhide Sato

Biomedicines 2022, 10(7), 1662; https://doi.org/10.3390/biomedicines10071662 - 11 Jul 2022

Cited by 7 | Viewed by 2019

Abstract

The conventional treatment of thoracic tumors includes surgery, anticancer drugs, radiation, and cancer immunotherapy. Light therapy for thoracic tumors has long been used as an alternative; conventional light therapy also called photodynamic therapy (PDT) has been used mainly for early-stage lung cancer. Recently, [...] Read more.

The conventional treatment of thoracic tumors includes surgery, anticancer drugs, radiation, and cancer immunotherapy. Light therapy for thoracic tumors has long been used as an alternative; conventional light therapy also called photodynamic therapy (PDT) has been used mainly for early-stage lung cancer. Recently, near-infrared photoimmunotherapy (NIR-PIT), which is a completely different concept from conventional PDT, has been developed and approved in Japan for the treatment of recurrent and previously treated head and neck cancer because of its specificity and effectiveness. NIR-PIT can apply to any target by changing to different antigens. In recent years, it has become clear that various specific and promising targets are highly expressed in thoracic tumors. In combination with these various specific targets, NIR-PIT is expected to be an ideal therapeutic approach for thoracic tumors. Additionally, techniques are being developed to further develop NIR-PIT for clinical practice. In this review, NIR-PIT is introduced, and its potential therapeutic applications for thoracic cancers are described. Full article

(This article belongs to the Topic Photodynamic Therapy)

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10 pages, 1492 KiB  

Open AccessReview

Cellular Mechanisms in Acute and Chronic Wounds after PDT Therapy: An Update

by Vieri Grandi, Alessandro Corsi, Nicola Pimpinelli and Stefano Bacci

Biomedicines 2022, 10(7), 1624; https://doi.org/10.3390/biomedicines10071624 - 07 Jul 2022

Cited by 14 | Viewed by 2499

Abstract

PDT is a two-stage treatment that combines light energy with a photosensitizer designed to destroy cancerous and precancerous cells after light activation. Photosensitizers are activated by a specific wavelength of light energy, usually from a laser. The photosensitizer is nontoxic until it is [...] Read more.

PDT is a two-stage treatment that combines light energy with a photosensitizer designed to destroy cancerous and precancerous cells after light activation. Photosensitizers are activated by a specific wavelength of light energy, usually from a laser. The photosensitizer is nontoxic until it is activated by light. However, after light activation, the photosensitizer becomes toxic to the targeted tissue. Among sensitizers, the topical use of ALA, a natural precursor of protoporphyrin IX, a precursor of the heme group, and a powerful photosensitizing agent, represents a turning point for PDT in the dermatological field, as it easily absorbable by the skin. Wound healing requires a complex interaction and coordination of different cells and molecules. Any alteration in these highly coordinated events can lead to either delayed or excessive healing. The goal of this review is to elucidate the cellular mechanisms involved, upon treatment with ALA-PDT, in chronic wounds, which are often associated with social isolation and high costs in terms of care. Full article

(This article belongs to the Topic Photodynamic Therapy)

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19 pages, 38145 KiB  

Open AccessArticle

Far-Infrared Therapy Decreases Orthotopic Allograft Transplantation Vasculopathy

by Yi-Wen Lin, Chien-Sung Tsai, Chun-Yao Huang, Yi-Ting Tsai, Chun-Ming Shih, Shing-Jong Lin, Chi-Yuan Li, Cheng-Yen Lin, Shih-Ying Sung and Feng-Yen Lin

Biomedicines 2022, 10(5), 1089; https://doi.org/10.3390/biomedicines10051089 - 07 May 2022

Cited by 3 | Viewed by 1989

Abstract

Orthotopic allograft transplantation (OAT) is a major strategy for solid heart and kidney failure. However, the recipient’s immunity-induced chronic rejection induces OAT vasculopathy that results in donor organ failure. With the exception of immunosuppressive agents, there are currently no specific means to inhibit [...] Read more.

Orthotopic allograft transplantation (OAT) is a major strategy for solid heart and kidney failure. However, the recipient’s immunity-induced chronic rejection induces OAT vasculopathy that results in donor organ failure. With the exception of immunosuppressive agents, there are currently no specific means to inhibit the occurrence of OAT vasculopathy. On the other hand, far-infrared (FIR) therapy uses low-power electromagnetic waves given by FIR, with a wavelength of 3–25 μm, to improve human physiological functions. Previous studies have shown that FIR therapy can effectively inhibit inflammation. It has also been widely used in adjuvant therapy for various clinical diseases, especially cardiovascular diseases, in recent years. Thus, we used this study to explore the feasibility of FIR in preventing OAT vasculopathy. In this study, the model of transplantation of an aorta graft from PVG/Seac rat to ACI/NKyo rat, and in vitro model of human endothelial progenitor cells (EPCs) was used. In this report, we presented that FIR therapy decreased the serious of vasculopathy in OAT-recipient ACI/NKyo rats via inhibiting proliferation of smooth muscle cells, accumulation of collagen, and infiltration of fibroblast in the vessel wall; humoral and cell-mediated immune responses were decreased in the spleen. The production of inflammatory proteins/cytokines also decreased in the plasma. Additionally, FIR therapy presented higher mobilization and circulating EPC levels associated with vessel repair in OAT-recipient ACI/NKyo rats. In vitro studies demonstrated that the underlying mechanisms of FIR therapy inhibiting OAT vasculopathy may be associated with the inhibition of the Smad2-Slug axis endothelial mesenchymal transition (EndoMT). Thus, FIR therapy may be the strategy to prevent chronic rejection-induced vasculopathy. Full article

(This article belongs to the Topic Photodynamic Therapy)

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17 pages, 2106 KiB  

Open AccessArticle

Antimicrobial Behavior and Cytotoxicity of Indocyanine Green in Combination with Visible Light and Water-Filtered Infrared A Radiation against Periodontal Bacteria and Subgingival Biofilm

by Diana Lorena Guevara Solarte, Sibylle Johanna Rau, Elmar Hellwig, Kirstin Vach and Ali Al-Ahmad

Biomedicines 2022, 10(5), 956; https://doi.org/10.3390/biomedicines10050956 - 20 Apr 2022

Cited by 6 | Viewed by 1924

Abstract

The widespread increase of antibiotic resistance highlights the need for alternative treatments such as antimicrobial photodynamic therapy (aPDT). This study aimed to evaluate the antimicrobial behavior and cytotoxicity of aPDT with indocyanine green (ICG) in combination with visible light (Vis) and water-filtered infrared [...] Read more.

The widespread increase of antibiotic resistance highlights the need for alternative treatments such as antimicrobial photodynamic therapy (aPDT). This study aimed to evaluate the antimicrobial behavior and cytotoxicity of aPDT with indocyanine green (ICG) in combination with visible light (Vis) and water-filtered infrared A (wIRA). Representative periodontal bacteria (Parvimonas micra, Atopobium riame, Slackia exigua, Actinomyces naeslundii, Porphyromonas gingivalis, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, and Prevotella nigrescens) and subgingival in situ biofilms from periodontal patients were treated with aPDT for 5 min. ICG was used at different concentrations (50–500 µg/mL) and the number of viable cells was determined in colony forming units (CFU). Untreated negative controls and 0.2% chlorhexidine as a positive control were also prepared. The cytotoxicity test on human keratinocytes in vitro was analyzed with the AlamarBlue assay after 5, 10, and 20 min, with four ICG concentrations, and at two temperatures (room temperature and 37 °C). The tested periodontal pathogens treated with aPDT were eliminated in a range between 1.2 and 6.7 log₁₀ CFU, except for A. naeslundii, which was killed at a lower range. The subgingival biofilm treated with aPDT expressed significant differences to the untreated controls except for at 300 µg/mL ICG concentration. The cytotoxicity was directly related to the concentration of ICG and irradiation time. These observations raise questions concerning the use of this specific aPDT as an adjuvant to periodontal treatments due to its possible toxicity towards human gingival cells. Full article

(This article belongs to the Topic Photodynamic Therapy)

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16 pages, 6476 KiB  

Open AccessArticle

Photodynamic Therapy in Combination with Doxorubicin Is Superior to Monotherapy for the Treatment of Lung Cancer

by Joseph C. Cacaccio, Farukh A. Durrani, Joseph R. Missert and Ravindra K. Pandey

Biomedicines 2022, 10(4), 857; https://doi.org/10.3390/biomedicines10040857 - 06 Apr 2022

Cited by 10 | Viewed by 2118

Abstract

We have previously shown that a radioactive (¹²³I)-analog of methyl 3-(1′-(iodobexyloxy) ethyl-3-devinylpyropheophorbide-a (PET-ONCO), derived from chlorophyll-a can be used for positron emission tomography (PET) imaging of a variety of tumors, including those where ¹⁸F-FDG shows limitations. In this study, the [...] Read more.

We have previously shown that a radioactive (¹²³I)-analog of methyl 3-(1′-(iodobexyloxy) ethyl-3-devinylpyropheophorbide-a (PET-ONCO), derived from chlorophyll-a can be used for positron emission tomography (PET) imaging of a variety of tumors, including those where ¹⁸F-FDG shows limitations. In this study, the photodynamic therapy (PDT) efficacy of the corresponding non-radioactive photosensitizer (PS) was investigated in a variety of tumor types (NSCLC, SCC, adenocarcinoma) derived from lung cancer patients in mice tumor models. The in vitro and in vivo efficacy was also investigated in combination with doxorubicin, and a significantly enhanced long-term tumor response was observed. The toxicity and toxicokinetic profile of the iodinated PS was also evaluated in male and female Sprague-Dawley rats and Beagle dog at variable doses (single intravenous injections) to assess reversibility or latency of any effects over a 28-day dose free period. The no-observed-adverse-effect (NOAEL) of the PS was considered to be 6.5 mg/kg for male and female rats, and for dogs, 3.45 mg/kg, the highest dose levels evaluated, respectively. The corresponding plasma C_max and AYC_last for male and female rats were 214,000 and 229,000 ng/mL and 3,680,000 and 3,810,000 h * ng/mL, respectively. For male and female dogs, the corresponding plasma C_max and AYC_last were 76,000 and 92,400 ng/mL and 976,000 and 1,200,000 h * ng/mL, respectively. Full article

(This article belongs to the Topic Photodynamic Therapy)

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16 pages, 4827 KiB  

Open AccessArticle

Antitumor Effect and Induced Immune Response Following Exposure of Hexaminolevulinate and Blue Light in Combination with Checkpoint Inhibitor in an Orthotopic Model of Rat Bladder Cancer

by Laureline Lamy, Jacques Thomas, Agnès Leroux, Jean-François Bisson, Kari Myren, Aslak Godal, Gry Stensrud and Lina Bezdetnaya

Biomedicines 2022, 10(3), 548; https://doi.org/10.3390/biomedicines10030548 - 25 Feb 2022

Cited by 5 | Viewed by 2533

Abstract

Previous studies have found that use of hexaminolevulinate (HAL) and blue light cystoscopy (BLC) during treatment of bladder cancer had a positive impact on overall survival after later cystectomy, indicating a potential treatment effect beyond improved diagnostic accuracy. The aim of our study [...] Read more.

Previous studies have found that use of hexaminolevulinate (HAL) and blue light cystoscopy (BLC) during treatment of bladder cancer had a positive impact on overall survival after later cystectomy, indicating a potential treatment effect beyond improved diagnostic accuracy. The aim of our study was to determine whether HAL and BL mimicking clinically relevant doses in an orthotopic rat model could have therapeutic effect by inducing modulation of a tumor-specific immune response. We also assessed whether administration with a checkpoint inhibitor could potentiate any effects observed. Rats were subjected to HAL BL alone and in combination with anti-PD-L1 and assessed for anti-tumor effects and effects on immune markers. Positive anti-tumor effect was observed in 63% and 31% of rats after, respectively, 12 and 30 days after the procedure, together with a localization effect of CD3+ and CD8+ cells after 30 days. Anti-tumor effect at 30 days increases from 31% up to 38% when combined with intravesical anti-PD-L1. In conclusion, our study demonstrated treatment effects with indications of systemic immune activation at diagnostic doses of HAL and blue light. The observed treatment effect seemed to be enhanced when used in combination with intravesically administrated immune checkpoint inhibitor. Full article

(This article belongs to the Topic Photodynamic Therapy)

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18 pages, 3114 KiB  

Open AccessArticle

Amphiphilic Protoporphyrin IX Derivatives as New Photosensitizing Agents for the Improvement of Photodynamic Therapy

by Stéphane Desgranges, Petras Juzenas, Vlada Vasovic, Odrun Arna Gederaas, Mikael Lindgren, Trond Warloe, Qian Peng and Christiane Contino-Pépin

Biomedicines 2022, 10(2), 423; https://doi.org/10.3390/biomedicines10020423 - 10 Feb 2022

Cited by 7 | Viewed by 2024

Abstract

Photodynamic therapy (PDT) is a non-invasive therapeutic modality based on the interaction between a photosensitive molecule called photosensitizer (PS) and visible light irradiation in the presence of oxygen molecule. Protoporphyrin IX (PpIX), an efficient and widely used PS, is hampered in clinical PDT [...] Read more.

Photodynamic therapy (PDT) is a non-invasive therapeutic modality based on the interaction between a photosensitive molecule called photosensitizer (PS) and visible light irradiation in the presence of oxygen molecule. Protoporphyrin IX (PpIX), an efficient and widely used PS, is hampered in clinical PDT by its poor water-solubility and tendency to self-aggregate. These features are strongly related to the PS hydrophilic–lipophilic balance. In order to improve the chemical properties of PpIX, a series of amphiphilic PpIX derivatives endowed with PEG₅₅₀ headgroups and hydrogenated or fluorinated tails was synthetized. Hydrophilic–lipophilic balance (HLB) and log p-values were computed for all of the prepared compounds. Their photochemical properties (spectroscopic characterization, photobleaching, and singlet oxygen quantum yield) were also evaluated followed by the in vitro studies of their cellular uptake, subcellular localization, and photocytotoxicity on three tumor cell lines (4T1, scc-U8, and WiDr cell lines). The results confirm the therapeutic potency of these new PpIX derivatives. Indeed, while all of the derivatives were perfectly water soluble, some of them exhibited an improved photodynamic effect compared to the parent PpIX. Full article

(This article belongs to the Topic Photodynamic Therapy)

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19 pages, 2643 KiB  

Open AccessArticle

N-Doped Graphene Quantum Dots/Titanium Dioxide Nanocomposites: A Study of ROS-Forming Mechanisms, Cytotoxicity and Photodynamic Therapy

by Pravena Ramachandran, Boon-Keat Khor, Chong Yew Lee, Ruey-An Doong, Chern Ein Oon, Nguyen Thi Kim Thanh and Hooi Ling Lee

Biomedicines 2022, 10(2), 421; https://doi.org/10.3390/biomedicines10020421 - 10 Feb 2022

Cited by 11 | Viewed by 3109

Abstract

Titanium dioxide nanoparticles (TiO₂ NPs) have been proven to be potential candidates in cancer therapy, particularly photodynamic therapy (PDT). However, the application of TiO₂ NPs is limited due to the fast recombination rate of the electron (e⁻)/hole (h⁺ [...] Read more.

Titanium dioxide nanoparticles (TiO₂ NPs) have been proven to be potential candidates in cancer therapy, particularly photodynamic therapy (PDT). However, the application of TiO₂ NPs is limited due to the fast recombination rate of the electron (e⁻)/hole (h⁺) pairs attributed to their broader bandgap energy. Thus, surface modification has been explored to shift the absorption edge to a longer wavelength with lower e⁻/h⁺ recombination rates, thereby allowing penetration into deep-seated tumors. In this study, TiO₂ NPs and N-doped graphene quantum dots (QDs)/titanium dioxide nanocomposites (N-GQDs/TiO₂ NCs) were synthesized via microwave-assisted synthesis and the two-pot hydrothermal method, respectively. The synthesized anatase TiO₂ NPs were self-doped TiO₂ (Ti³⁺ ions), have a small crystallite size (12.2 nm) and low bandgap energy (2.93 eV). As for the N-GQDs/TiO₂ NCs, the shift to a bandgap energy of 1.53 eV was prominent as the titanium (IV) tetraisopropoxide (TTIP) loading increased, while maintaining the anatase tetragonal crystal structure with a crystallite size of 11.2 nm. Besides, the cytotoxicity assay showed that the safe concentrations of the nanomaterials were from 0.01 to 0.5 mg mL⁻¹. Upon the photo-activation of N-GQDs/TiO₂ NCs with near-infrared (NIR) light, the nanocomposites generated reactive oxygen species (ROS), mainly singlet oxygen (¹O₂), which caused more significant cell death in MDA-MB-231 (an epithelial, human breast cancer cells) than in HS27 (human foreskin fibroblast). An increase in the N-GQDs/TiO₂ NCs concentrations elevates ROS levels, which triggered mitochondria-associated apoptotic cell death in MDA-MB-231 cells. As such, titanium dioxide-based nanocomposite upon photoactivation has a good potential as a photosensitizer in PDT for breast cancer treatment. Full article

(This article belongs to the Topic Photodynamic Therapy)

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10 pages, 1040 KiB  

Open AccessArticle

Photodynamic Inactivation of Antibiotic-Resistant and Sensitive Aeromonas hydrophila with Peripheral Pd(II)- vs. Zn(II)-Phthalocyanines

by Vanya N. Mantareva, Vesselin Kussovski, Petya Orozova, Lyudmila Dimitrova, Irem Kulu, Ivan Angelov, Mahmut Durmus and Hristo Najdenski

Biomedicines 2022, 10(2), 384; https://doi.org/10.3390/biomedicines10020384 - 05 Feb 2022

Cited by 10 | Viewed by 1862

Abstract

The antimicrobial multidrug resistance (AMR) of pathogenic bacteria towards currently used antibiotics has a remarkable impact on the quality and prolongation of human lives. An effective strategy to fight AMR is the method PhotoDynamic Therapy (PDT). PDT is based on a joint action [...] Read more.

The antimicrobial multidrug resistance (AMR) of pathogenic bacteria towards currently used antibiotics has a remarkable impact on the quality and prolongation of human lives. An effective strategy to fight AMR is the method PhotoDynamic Therapy (PDT). PDT is based on a joint action of a photosensitizer, oxygen, and light within a specific spectrum. This results in the generation of singlet oxygen and other reactive oxygen species that can inactivate the pathogenic cells without further regrowth. This study presents the efficacy of a new Pd(II)- versus Zn(II)-phthalocyanine complexes with peripheral positions of methylpyridiloxy substitution groups (pPdPc and ZnPcMe) towards Gram-negative bacteria Aeromonas hydrophila (A.hydrophila). Zn(II)-phthalocyanine, ZnPcMe was used as a reference compound for in vitro studies, bacause it is well-known with a high photodynamic inactivation ability for different pathogenic microorganisms. The studied new isolates of A.hydrophila were antibiotic-resistant (R) and sensitive (S) strains. The photoinactivation results showed a full effect with 8 µM pPdPc for S strain and with 5 µM ZnPcMe for both R and S strains. Comparison between both new isolates of A.hydrophila (S and R) suggests that the uptakes and more likely photoinactivation efficacy of the applied phthalocyanines are independent of the drug sensitivity of the studied strains. Full article

(This article belongs to the Topic Photodynamic Therapy)

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13 pages, 3535 KiB  

Open AccessArticle

Photodynamic Effects with 5-Aminolevulinic Acid on Cytokines and Exosomes in Human Peripheral Blood Mononuclear Cells

by Kristian Espeland, Andrius Kleinauskas, Petras Juzenas, Andreas Brech, Sagar Darvekar, Vlada Vasovic, Trond Warloe, Eidi Christensen, Jørgen Jahnsen and Qian Peng

Biomedicines 2022, 10(2), 232; https://doi.org/10.3390/biomedicines10020232 - 21 Jan 2022

Cited by 4 | Viewed by 2901

Abstract

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor to the potent photosensitizer, protoporphyrin IX (PpIX), is an established modality for several malignant and premalignant diseases. This treatment is based on the light-activated PpIX in targeted lesions. Although numerous studies have confirmed the [...] Read more.

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), a precursor to the potent photosensitizer, protoporphyrin IX (PpIX), is an established modality for several malignant and premalignant diseases. This treatment is based on the light-activated PpIX in targeted lesions. Although numerous studies have confirmed the necrosis and apoptosis involved in the mechanism of action of this modality, little information is available for the change of exosome levels after treatment. We report from the first study on the effects of ALA-PDT on cytokines and exosomes of human healthy peripheral blood mononuclear cells (PBMCs). The treatment reduced the cytokines and exosomes studied, although there was variation among individual PBMC samples. This reduction is consistent with PDT-mediated survivals of subsets of PBMCs. More specifically, the ALA-PDT treatment apparently decreased all pro-inflammatory cytokines included, suggesting that this treatment may provide a strong anti-inflammatory effect. In addition, the treatment has decreased the levels of different types of exosomes, the HLA-DRDPDQ exosome in particular, which plays an important role in the rejection of organ transplantation as well as autoimmune diseases. These results may suggest future therapeutic strategies of ALA-PDT. Full article

(This article belongs to the Topic Photodynamic Therapy)

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10 pages, 2802 KiB  

Open AccessReview

Perspectives on Light-Based Disinfection to Reduce the Risk of COVID-19 Transmission during Dental Care

by Abdulrahman A. Balhaddad, Lamia Mokeem, Sharukh S. Khajotia, Fernando L. Esteban Florez and Mary A. S. Melo

BioMed 2022, 2(1), 27-36; https://doi.org/10.3390/biomed2010003 - 10 Jan 2022

Cited by 2 | Viewed by 2925

Abstract

Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) is a positive-sense single-stranded RNA coronavirus capable of causing potentially lethal pneumonia-like infectious diseases in mammals and birds. The main mechanisms by which SARS-CoV-2 spreads include airborne transmission (aerosols and droplets) and the direct exposure of tissues [...] Read more.

Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) is a positive-sense single-stranded RNA coronavirus capable of causing potentially lethal pneumonia-like infectious diseases in mammals and birds. The main mechanisms by which SARS-CoV-2 spreads include airborne transmission (aerosols and droplets) and the direct exposure of tissues (conjunctival, nasal, and oral mucosa) to contaminated fluids. The aerosol formation is universal in dentistry due to the use of rotary instruments (handpieces), ultrasonic scalers, and air–water syringes. Several layers of infection control should protect key stakeholders such as dentists, dental staff, and patients. These include the utilization of personal protective equipment, high-volume evacuation systems, pre-procedural mouthwashes, rubber dam, and more recently, antimicrobial photodynamic therapy and intra-oral visible light irradiation. These non-specific light-based approaches are relatively simple, inexpensive, and effective against viruses, bacteria, and fungi. Therefore, the present perspective review discusses the current efforts and limitations on utilizing biophotonic approaches as adjunct infection control methods to prevent the transmission of SARS-CoV-2 in dental settings. In addition, the present perspective review may positively impact subsequent developments in the field, as it offers relevant information regarding the intricacies and complexities of infection control in dental settings. Full article

(This article belongs to the Topic Photodynamic Therapy)

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14 pages, 20938 KiB  

Open AccessArticle

Photodynamic Therapy (PDT) in Prosthodontics: Disinfection of Human Teeth Exposed to Streptococcus mutans and the Effect on the Adhesion of Full Ceramic Veneers, Crowns, and Inlays: An In Vitro Study

by Corina Elena Tisler, Radu Chifor, Mindra Eugenia Badea, Marioara Moldovan, Doina Prodan, Rahela Carpa, Stanca Cuc, Ioana Chifor and Alexandru Florin Badea

Biomedicines 2022, 10(1), 144; https://doi.org/10.3390/biomedicines10010144 - 10 Jan 2022

Cited by 3 | Viewed by 1972

Abstract

The use of PDT in prosthodontics as a disinfection protocol can eradicate bacteria from tooth surfaces by causing the death of the microorganisms to which the photosensitizer binds, absorbing the energy of laser light during irradiation. The aim of the study was to [...] Read more.

The use of PDT in prosthodontics as a disinfection protocol can eradicate bacteria from tooth surfaces by causing the death of the microorganisms to which the photosensitizer binds, absorbing the energy of laser light during irradiation. The aim of the study was to investigate the capacity of PDT to increase the bond strength of full ceramic restorations. In this study, 45 extracted human teeth were prepared for veneers, crowns, and inlays and contaminated with Streptococcus mutans. Tooth surfaces decontamination was performed using a diode laser and methylene blue as a photosensitizer. The disinfection effect and the impact on tensile bond strength were evaluated by scanning electron microscopy (SEM) and pull-out tests of the cemented ceramic prosthesis. Results show that the number of bacteria was reduced from colonized prepared tooth surfaces, and the bond strength was increased when PDT was used. In conclusion, the present study indicates that using PDT as a protocol before the final adhesive cementation of ceramic restorations could be a promising approach, with outstanding advantages over conventional methods. Full article

(This article belongs to the Topic Photodynamic Therapy)

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13 pages, 2801 KiB  

Open AccessArticle

Chlorin Endogenous to the North Pacific Brittle Star Ophiura sarsii for Photodynamic Therapy Applications in Breast Cancer and Glioblastoma Models

by Antonina Klimenko, Elvira E. Rodina, Denis Silachev, Maria Begun, Valentina A. Babenko, Anton S. Benditkis, Anton S. Kozlov, Alexander A. Krasnovsky, Yuri S. Khotimchenko and Vladimir L. Katanaev

Biomedicines 2022, 10(1), 134; https://doi.org/10.3390/biomedicines10010134 - 08 Jan 2022

Cited by 3 | Viewed by 1918

Abstract

Photodynamic therapy (PDT) represents a powerful avenue for anticancer treatment. PDT relies on the use of photosensitizers—compounds accumulating in the tumor and converted from benign to cytotoxic upon targeted photoactivation. We here describe (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (ETPA) as a major [...] Read more.

Photodynamic therapy (PDT) represents a powerful avenue for anticancer treatment. PDT relies on the use of photosensitizers—compounds accumulating in the tumor and converted from benign to cytotoxic upon targeted photoactivation. We here describe (3S,4S)-14-Ethyl-9-(hydroxymethyl)-4,8,13,18-tetramethyl-20-oxo-3-phorbinepropanoic acid (ETPA) as a major metabolite of the North Pacific brittle stars Ophiura sarsii. As a chlorin, ETPA efficiently produces singlet oxygen upon red-light photoactivation and exerts powerful sub-micromolar phototoxicity against a panel of cancer cell lines in vitro. In a mouse model of glioblastoma, intravenous ETPA injection combined with targeted red laser irradiation induced strong necrotic ablation of the brain tumor. Along with the straightforward ETPA purification protocol and abundance of O. sarsii, these studies pave the way for the development of ETPA as a novel natural product-based photodynamic therapeutic. Full article

(This article belongs to the Topic Photodynamic Therapy)

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26 pages, 2392 KiB  

Open AccessReview

Nanomedicine in Clinical Photodynamic Therapy for the Treatment of Brain Tumors

by Hyung Shik Kim and Dong Yun Lee

Biomedicines 2022, 10(1), 96; https://doi.org/10.3390/biomedicines10010096 - 03 Jan 2022

Cited by 14 | Viewed by 4975

Abstract

The current treatment for malignant brain tumors includes surgical resection, radiotherapy, and chemotherapy. Nevertheless, the survival rate for patients with glioblastoma multiforme (GBM) with a high grade of malignancy is less than one year. From a clinical point of view, effective treatment of [...] Read more.

The current treatment for malignant brain tumors includes surgical resection, radiotherapy, and chemotherapy. Nevertheless, the survival rate for patients with glioblastoma multiforme (GBM) with a high grade of malignancy is less than one year. From a clinical point of view, effective treatment of GBM is limited by several challenges. First, the anatomical complexity of the brain influences the extent of resection because a fine balance must be struck between maximal removal of malignant tissue and minimal surgical risk. Second, the central nervous system has a distinct microenvironment that is protected by the blood–brain barrier, restricting systemically delivered drugs from accessing the brain. Additionally, GBM is characterized by high intra-tumor and inter-tumor heterogeneity at cellular and histological levels. This peculiarity of GBM-constituent tissues induces different responses to therapeutic agents, leading to failure of targeted therapies. Unlike surgical resection and radiotherapy, photodynamic therapy (PDT) can treat micro-invasive areas while protecting sensitive brain regions. PDT involves photoactivation of photosensitizers (PSs) that are selectively incorporated into tumor cells. Photo-irradiation activates the PS by transfer of energy, resulting in production of reactive oxygen species to induce cell death. Clinical outcomes of PDT-treated GBM can be advanced in terms of nanomedicine. This review discusses clinical PDT applications of nanomedicine for the treatment of GBM. Full article

(This article belongs to the Topic Photodynamic Therapy)

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17 pages, 3877 KiB  

Open AccessArticle

Autophagy and Apoptosis Induced in U87 MG Glioblastoma Cells by Hypericin-Mediated Photodynamic Therapy Can Be Photobiomodulated with 808 nm Light

by Viktoria Pevna, Georges Wagnières and Veronika Huntosova

Biomedicines 2021, 9(11), 1703; https://doi.org/10.3390/biomedicines9111703 - 17 Nov 2021

Cited by 13 | Viewed by 2793

Abstract

Glioblastoma is one of the most aggressive types of tumors. Although few treatment options are currently available, new modalities are needed to improve prognosis. In this context, photodynamic therapy (PDT) is a promising adjuvant treatment modality. In the present work, hypericin-mediated PDT (hypericin-PDT, [...] Read more.

Glioblastoma is one of the most aggressive types of tumors. Although few treatment options are currently available, new modalities are needed to improve prognosis. In this context, photodynamic therapy (PDT) is a promising adjuvant treatment modality. In the present work, hypericin-mediated PDT (hypericin-PDT, 2 J/cm²) of U87 MG cells is combined with (2 min, 15 mW/cm² at 808 nm) photobiomodulation (PBM). We observed that PBM stimulates autophagy, which, in combination with PDT, increases the treatment efficacy and leads to apoptosis. Confocal fluorescence microscopy, cytotoxicity assays and Western blot were used to monitor apoptotic and autophagic processes in these cells. Destabilization of lysosomes, mitochondria and the Golgi apparatus led to an increase in lactate dehydrogenase activity, oxidative stress levels, LC3-II, and caspase-3, as well as a decrease of the PKCα and STAT3 protein levels in response to hypericin-PDT subcellular concentration in U87 MG cells. Our results indicate that therapeutic hypericin concentrations can be reduced when PDT is combined with PBM. This will likely allow to reduce the damage induced in surrounding healthy tissues when PBM-hypericin-PDT is used for in vivo tumor treatments. Full article

(This article belongs to the Topic Photodynamic Therapy)

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15 pages, 4060 KiB  

Open AccessArticle

Styrene Maleic Acid Copolymer-Based Micellar Formation of Temoporfin (SMA@ mTHPC) Behaves as A Nanoprobe for Tumor-Targeted Photodynamic Therapy with A Superior Safety

by Jun Fang, Shanghui Gao, Rayhanul Islam, Hinata Nema, Rina Yanagibashi, Niho Yoneda, Natsumi Watanabe, Yuki Yasuda, Naoki Nuita, Jian-Rong Zhou and Kazumi Yokomizo

Biomedicines 2021, 9(10), 1493; https://doi.org/10.3390/biomedicines9101493 - 19 Oct 2021

Cited by 9 | Viewed by 2428

Abstract

Tumor-targeted photodynamic therapy (PDT) using polymeric photosensitizers is a promising anticancer therapeutic strategy. Previously, we developed several polymeric nanoprobes for PDT using different polymers and PDT agents. In the study, we synthesized a styrene maleic acid copolymer (SMA) micelle encapsulating temoporfin (mTHPC) that [...] Read more.

Tumor-targeted photodynamic therapy (PDT) using polymeric photosensitizers is a promising anticancer therapeutic strategy. Previously, we developed several polymeric nanoprobes for PDT using different polymers and PDT agents. In the study, we synthesized a styrene maleic acid copolymer (SMA) micelle encapsulating temoporfin (mTHPC) that is a clinically used PDT drug, SMA@mTHPC, with a hydrodynamic size of 98 nm, which showed high water solubility. SMA@mTHPC maintained stable micelle formation in physiological aqueous solutions including serum; however, the micelles could be disrupted in the presence of detergent (e.g., Tween 20) as well as lecithin, the major component of cell membrane, suggesting micelles will be destroyed and free mTHPC will be released during intracellular uptake. SMA@mTHPC showed a pH-dependent release profile, for which a constant release of ≈20% per day was found at pH 7.4, and much more release occurred at acidic pH (e.g., 6.5, 5.5), suggesting extensive release of free mTHPC could occur in the weak acidic environment of a tumor and further during internalization into tumor cells. In vitro cytotoxicity assay showed a lower cytotoxicity of SMA@mTHPC than free mTHPC; however, similar in vivo antitumor effects were observed by both SMA@mTHPC and free THPC. More importantly, severe side effects (e.g., body weight loss, death of the mice) were found during free mTHPC treatment, whereas no apparent side effects were observed for SMA@mTHPC. The superior safety profile of SMA@mTHPC was mostly due to its micelle formation and the enhanced permeability and retention (EPR) effect-based tumor accumulation, as well as the tumor environment-responsive release properties. These findings suggested SMA@mTHPC may become a good candidate drug for targeted PDT with high safety. Full article

(This article belongs to the Topic Photodynamic Therapy)

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17 pages, 5291 KiB  

Open AccessArticle

Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM)

by Alex Vasilev, Roba Sofi, Stuart J. Smith, Ruman Rahman, Anja G. Teschemacher and Sergey Kasparov

Biomedicines 2021, 9(10), 1453; https://doi.org/10.3390/biomedicines9101453 - 13 Oct 2021

Cited by 8 | Viewed by 2190

Abstract

One of the most challenging problems in the treatment of glioblastoma (GBM) is the highly infiltrative nature of the disease. Infiltrating cells that are non-resectable are left behind after debulking surgeries and become a source of regrowth and recurrence. To prevent tumor recurrence [...] Read more.

One of the most challenging problems in the treatment of glioblastoma (GBM) is the highly infiltrative nature of the disease. Infiltrating cells that are non-resectable are left behind after debulking surgeries and become a source of regrowth and recurrence. To prevent tumor recurrence and increase patient survival, it is necessary to cleanse the adjacent tissue from GBM infiltrates. This requires an innovative local approach. One such approach is that of photodynamic therapy (PDT) which uses specific light-sensitizing agents called photosensitizers. Here, we show that tetramethylrhodamine methyl ester (TMRM), which has been used to asses mitochondrial potential, can be used as a photosensitizer to target GBM cells. Primary patient-derived GBM cell lines were used, including those specifically isolated from the infiltrative edge. PDT with TMRM using low-intensity green light induced mitochondrial damage, an irreversible drop in mitochondrial membrane potential and led to GBM cell death. Moreover, delayed photoactivation after TMRM loading selectively killed GBM cells but not cultured rat astrocytes. The efficacy of TMRM-PDT in certain GBM cell lines may be potentiated by adenylate cyclase activator NKH477. Together, these findings identify TMRM as a prototypical mitochondrially targeted photosensitizer with beneficial features which may be suitable for preclinical and clinical translation. Full article

(This article belongs to the Topic Photodynamic Therapy)

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16 pages, 3488 KiB  

Open AccessEditor’s ChoiceArticle

Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect

by Carla M. Magalhães, Patricia González-Berdullas, Diana Duarte, Ana Salomé Correia, José E. Rodríguez-Borges, Nuno Vale, Joaquim C. G. Esteves da Silva and Luís Pinto da Silva

Biomedicines 2021, 9(9), 1199; https://doi.org/10.3390/biomedicines9091199 - 11 Sep 2021

Cited by 22 | Viewed by 2367

Abstract

Photodynamic therapy (PDT) is an anticancer therapeutic modality with remarkable advantages over more conventional approaches. However, PDT is greatly limited by its dependence on external light sources. Given this, PDT would benefit from new systems capable of a light-free and intracellular photodynamic effect. [...] Read more.

Photodynamic therapy (PDT) is an anticancer therapeutic modality with remarkable advantages over more conventional approaches. However, PDT is greatly limited by its dependence on external light sources. Given this, PDT would benefit from new systems capable of a light-free and intracellular photodynamic effect. Herein, we evaluated the heavy-atom effect as a strategy to provide anticancer activity to derivatives of coelenterazine, a chemiluminescent single-molecule widespread in marine organisms. Our results indicate that the use of the heavy-atom effect allows these molecules to generate readily available triplet states in a chemiluminescent reaction triggered by a cancer marker. Cytotoxicity assays in different cancer cell lines showed a heavy-atom-dependent anticancer activity, which increased in the substituent order of hydroxyl < chlorine < bromine. Furthermore, it was found that the magnitude of this anticancer activity is also dependent on the tumor type, being more relevant toward breast and prostate cancer. The compounds also showed moderate activity toward neuroblastoma, while showing limited activity toward colon cancer. In conclusion, the present results indicate that the application of the heavy-atom effect to marine coelenterazine could be a promising approach for the future development of new and optimized self-activating and tumor-selective sensitizers for light-free PDT. Full article

(This article belongs to the Topic Photodynamic Therapy)

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16 pages, 4390 KiB  

Open AccessArticle

DNA Hypermethylation Involves in the Down-Regulation of Chloride Intracellular Channel 4 (CLIC4) Induced by Photodynamic Therapy

by Pei-Chi Chiang, Pei-Tzu Li, Ming-Jen Lee and Chin-Tin Chen

Biomedicines 2021, 9(8), 927; https://doi.org/10.3390/biomedicines9080927 - 31 Jul 2021

Cited by 1 | Viewed by 1577

Abstract

The altered expression of chloride intracellular channel 4 (CLIC4) was reported to correlate with tumor progression. Previously, we have shown that the reduced cellular invasion induced by photodynamic therapy (PDT) is associated with suppression of CLIC4 expression in PDT-treated cells. Herein, we attempted [...] Read more.

The altered expression of chloride intracellular channel 4 (CLIC4) was reported to correlate with tumor progression. Previously, we have shown that the reduced cellular invasion induced by photodynamic therapy (PDT) is associated with suppression of CLIC4 expression in PDT-treated cells. Herein, we attempted to decipher the regulatory mechanisms involved in PDT-mediated CLIC4 suppression in A375 and MDA-MB-231 cells in vitro. We found that PDT can increase the expression and enzymatic activity of DNA methyltransferase 1 (DNMT1). Bisulfite sequencing PCR further revealed that PDT can induce hypermethylation in the CLIC4 promoter region. Silencing DNMT1 rescues the PDT-induced CLIC4 suppression and inhibits hypermethylation in its promoter. Furthermore, we found tumor suppressor p53 involves in the increased DNMT1 expression of PDT-treated cells. Finally, by comparing CLIC4 expression in lung malignant cells and normal lung fibroblasts, the extent of methylation in CLIC4 promoter was found to be inversely proportional to its expression. Taken together, our results indicate that CLIC4 suppression induced by PDT is modulated by DNMT1-mediated hypermethylation and depends on the status of p53, which provides a possible mechanistic basis for regulating CLIC4 expression in tumorigenesis. Full article

(This article belongs to the Topic Photodynamic Therapy)

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