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Special Issue "Photodynamic Therapy"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Photochemistry".

Deadline for manuscript submissions: closed (31 October 2016)

Special Issue Editor

Guest Editor
Prof. Dr. Norbert Lange

School of Pharmaceutical Sciences Geneva-Lausanne, University of Geneva, University of Lausanne, Switzerland
Website | E-Mail
Interests: photodynamic therapy; photosensitizers; drug delivery; targeted PDT; prodrugs; disease diagnosis; cell death mechanisms; translational research; oncology

Special Issue Information

Dear Colleagues,

Photodynamic therapy (PDT) is based on the topical or systemic administration of a photosensitizer preferentially accumulated in a diseased target tissue. Irradiation of the diseased area triggers the production of toxic reactive oxygen species, subsequently leading to cell death. Furthermore, the photosensitizer’s ability to localize in diseases tissue can be used for the improved detection of disease because most of these molecules are intrinsically fluorescent. Most photosensitizers are based on porphyrins and phthalocyanines, though other chemical skeletons have been considered. Since its first description at the beginning of the 20th century, intensive research in PDT has provided profound insight into improved treatment modalities. Currently, PDT is developing intensively into other fields including bacterial inactivation and photochemical internalization.

Although not completely integrated into daily clinical practice in most areas, nowadays PDT represents of valid piece in today’s clinician’s toolbox for the curative and palliative treatment of several diseases, including head and neck cancer, age related macular degeneration, esophageal cancer, and skin cancer to name a few.

This special issue on photodynamic therapy is dedicated to the newest information in this research field. It should reflect a roundtable of the most proficient researches in photodynamic therapy. We expect an intensive debate and the latest findings on improved photosensitizers, innovative drug delivery strategies in PDT, and current and potential applications in clinical practice.

Prof. Dr. Norbert Lange
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (5 papers)

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Research

Open AccessArticle Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity
Molecules 2017, 22(3), 345; doi:10.3390/molecules22030345
Received: 4 January 2017 / Revised: 1 February 2017 / Accepted: 20 February 2017 / Published: 23 February 2017
Cited by 2 | PDF Full-text (2638 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers,
[...] Read more.
The efficiency of photodynamic therapy is limited mainly due to low selectivity, unfavorable biodistribution of photosensitizers, and long-lasting skin sensitivity to light. However, drug delivery systems based on nanoparticles may overcome the limitations mentioned above. Among others, dendrimers are particularly attractive as carriers, because of their globular architecture and high loading capacity. The goal of the study was to check whether an anionic phosphorus dendrimer is suitable as a carrier of a photosensitizer—methylene blue (MB). As a biological model, basal cell carcinoma cell lines were used. We checked the influence of the MB complexation on its singlet oxygen production ability using a commercial fluorescence probe. Next, cellular uptake, phototoxicity, reactive oxygen species (ROS) generation, and cell death were investigated. The MB-anionic dendrimer complex (MB-1an) was found to generate less singlet oxygen; however, the complex showed higher cellular uptake and phototoxicity against basal cell carcinoma cell lines, which was accompanied with enhanced ROS production. Owing to the obtained results, we conclude that the photodynamic activity of MB complexed with an anionic dendrimer is higher than free MB against basal cell carcinoma cell lines. Full article
(This article belongs to the Special Issue Photodynamic Therapy)
Figures

Open AccessArticle Preclinical Study of Antineoplastic Sinoporphyrin Sodium-PDT via In Vitro and In Vivo Models
Molecules 2017, 22(1), 112; doi:10.3390/molecules22010112
Received: 31 October 2016 / Revised: 26 December 2016 / Accepted: 4 January 2017 / Published: 11 January 2017
Cited by 1 | PDF Full-text (2534 KB) | HTML Full-text | XML Full-text
Abstract
Photodynamic therapy (PDT) investigations have seen stable increases and the development of new photosensitizers is a heated topic. Sinoporphyrin sodium is a new photosensitizer isolated from Photofrin. This article evaluated its anticancer effects by clonogenic assays, MTT assays and xenograft experiments in comparison
[...] Read more.
Photodynamic therapy (PDT) investigations have seen stable increases and the development of new photosensitizers is a heated topic. Sinoporphyrin sodium is a new photosensitizer isolated from Photofrin. This article evaluated its anticancer effects by clonogenic assays, MTT assays and xenograft experiments in comparison to Photofrin. The clonogenicity inhibition rates of sinoporphyrin sodium-PDT towards four human cancer cell lines ranged from 85.5% to 94.2% at 0.5 μg/mL under 630 nm irradiation of 30 mW/cm2 for 180 s. For MTT assays, the IC50 ranges of Photofrin-PDT and sinoporphyrin sodium-PDT towards human cancer cells were 0.3 μg/mL to 5.5 μg/mL and 0.1 μg/mL to 0.8 μg/mL under the same irradiation conditions, respectively. The IC50 values of Photofrin-PDT and sinoporphyrin sodium-PDT towards human skin cells, HaCaT, were 10 μg/mL and 1.0 μg/mL, respectively. Esophagus carcinoma and hepatoma xenograft models were established to evaluate the in vivo antineoplastic efficacy. A control group, Photofrin-PDT group (20 mg/kg) and sinoporphyrin sodium group at three doses, 0.5 mg/kg, 1 mg/kg and 2 mg/kg, were set. Mice were injected with photosensitizers 24 h before 60 J 630 nm laser irradiation. The tumor weight inhibition ratio of 2 mg/kg sinoporphyrin sodium-PDT reached approximately 90%. Besides, the tumor growths were significantly slowed down by 2 mg/kg sinoporphyrin sodium-PDT, which was equivalent to 20 mg/kg Photofrin-PDT. In sum, sinoporphyrin sodium-PDT showed great anticancer efficacy and with a smaller dose compared with Photofrin. Further investigations are warranted. Full article
(This article belongs to the Special Issue Photodynamic Therapy)
Figures

Figure 1

Open AccessArticle In Vitro Photodynamic Effect of Phycocyanin against Breast Cancer Cells
Molecules 2016, 21(11), 1470; doi:10.3390/molecules21111470
Received: 29 September 2016 / Accepted: 1 October 2016 / Published: 3 November 2016
Cited by 2 | PDF Full-text (5416 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
C-phycocyanin, a natural blue-colored pigment-protein complex was explored as a novel photosensitizer for use in low-level laser therapy under 625-nm laser illumination. C-phycocyanin produced singlet oxygen radicals and the level of reactive oxygen species (ROS) were raised in extended time of treatment. It
[...] Read more.
C-phycocyanin, a natural blue-colored pigment-protein complex was explored as a novel photosensitizer for use in low-level laser therapy under 625-nm laser illumination. C-phycocyanin produced singlet oxygen radicals and the level of reactive oxygen species (ROS) were raised in extended time of treatment. It did not exhibit any visible toxic effect in the absence of light. Under 625-nm laser irradiation, c-phycocyanin generated cytotoxic stress through ROS induction, which killed MDA-MB-231 breast cancer cells depending on concentrations. Different fluorescent staining of laser-treated cells explored apoptotic cell death characteristics like the shrinking of cells, cytoplasmic condensation, nuclei cleavage, and the formation of apoptotic bodies. In conclusion, phycocyanin is a non-toxic fluorescent pigment that can be used in low-level light therapy. Full article
(This article belongs to the Special Issue Photodynamic Therapy)
Figures

Open AccessArticle Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors
Molecules 2016, 21(10), 1347; doi:10.3390/molecules21101347
Received: 25 August 2016 / Revised: 6 October 2016 / Accepted: 7 October 2016 / Published: 12 October 2016
Cited by 3 | PDF Full-text (2521 KB) | HTML Full-text | XML Full-text
Abstract
We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of
[...] Read more.
We evaluated the potential utility of hydrogels for delivery of the photosensitizing agents 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) to rectal tumors. Hydrogel suppositories containing ALA or HMME were administered to the rectal cavity of BALB/c mice bearing subcutaneous tumors of SW837 rectal carcinoma cells. For comparison, ALA and HMME were also administered by three common photosensitizer delivery routes; local administration to the skin and intratumoral or intravenous injection. The concentration of ALA-induced protoporphyrin IX or HMME in the rectal wall, skin, and subcutaneous tumor was measured by fluorescence spectrophotometry, and their distribution in vertical sections of the tumor was measured using a fluorescence spectroscopy system. The concentration of ALA-induced protoporphyrin IX in the rectal wall after local administration of suppositories to the rectal cavity was 9.76-fold (1 h) and 5.8-fold (3 h) higher than in the skin after cutaneous administration. The maximal depth of ALA penetration in the tumor was ~3–6 mm at 2 h after cutaneous administration. Much lower levels of HMME were observed in the rectal wall after administration as a hydrogel suppository, and the maximal depth of tumor penetration was <2 mm after cutaneous administration. These data show that ALA more readily penetrates the mucosal barrier than the skin. Administration of ALA as an intrarectal hydrogel suppository is thus a potential delivery route for photodynamic therapy of rectal cancer. Full article
(This article belongs to the Special Issue Photodynamic Therapy)
Figures

Figure 1

Open AccessArticle Size-Dependent Photodynamic Anticancer Activity of Biocompatible Multifunctional Magnetic Submicron Particles in Prostate Cancer Cells
Molecules 2016, 21(9), 1187; doi:10.3390/molecules21091187
Received: 7 July 2016 / Revised: 18 August 2016 / Accepted: 31 August 2016 / Published: 6 September 2016
Cited by 3 | PDF Full-text (3810 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe2O4-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as a photosensitizer delivery agent for photodynamic therapy in cancer cells. To provide selective targeting
[...] Read more.
In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe2O4-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as a photosensitizer delivery agent for photodynamic therapy in cancer cells. To provide selective targeting of cancer cells and destruction of cancer cell functionality, basic cobalt ferrite (CoFe2O4) particles were covalently bonded with a photosensitizer (PS), which comprises hematoporphyrin (HP), and folic acid (FA) molecules. The magnetic properties of the CoFe2O4 particles were finely adjusted by controlling the size of the primary CoFe2O4 nanograins, and secondary superstructured composite particles were formed by aggregation of the nanograins. The prepared CoFe2O4-HP-FA exhibited high water solubility, good MR-imaging capacity, and biocompatibility without any in vitro cytotoxicity. In particular, our CoFe2O4-HP-FA exhibited remarkable photodynamic anticancer efficiency via induction of apoptotic death in PC-3 prostate cancer cells in a particle size- and concentration-dependent manner. This size-dependent effect was determined by the specific surface area of the particles because the number of HP molecules increased with decreasing size and increasing surface area. These results indicate that our CoFe2O4-HP-FA may be applicable for photodynamic therapy (PDT) as a PS delivery material and a therapeutic agent for MR-imaging based PDT owing to their high saturation value for magnetization and superparamagnetism. Full article
(This article belongs to the Special Issue Photodynamic Therapy)
Figures

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Photosensitizer Cd-Free Nanostructured Metal Chalcogenides for Cancer-Targeted Photodynamic Therapy
Authors: Juan Beltran-Huarac, Daysi Diaz-Diestra, Bibek Thapa, Brad R. Weiner and Gerardo Morell
Affiliation: Molecular Sciences Research Center, University of Puerto Rico, San Juan, PR 00926, USA
Abstract: Overcoming the inefficient delivery of light to specific photosensitizers (PSs) is a big challenge in cancer photodynamic therapy (PDT) since it hinders the clinical treatment of tumors located deep under the skin. In PDT, reactive oxygen species (ROSs) produced by irradiation cause the shutdown of vessels depriving the tumor of nutrients and oxygen, and in turn an adverse effect on the immune system. Nonetheless, although PDT offers a disease site-specific treatment modality the classic PSs based on a porphyrin-like nucleus exhibit some limitations, such as poor solubility in body fluids and injectable solvents, bad photostability, poor
amphilicity for tissue penetration, slow elimination from nontarget tissue (increasing skin photosensitivity) and significant systemic toxicity. Nanostructured materials (1–100 nm in size) as an emerging technology in the field of PDT have been demonstrated to circumvent most of such limitations. They can be artificially engineered to carry multiple theranostic agents to targeted tumor sites. However, recent studies on photosensitive Cd-based nanostructures (most widely used in PDT) indicate that the leeching of Cd2+ ions takes place as they are continuously exposed to harsh biological conditions, making them acutely toxic and hampering their in vivo applications. Since they are not completely immune to degradation, efforts have been devoted to seeking new alternatives. In this review, we focus on the recent developments of Cd-free nanostructured metal chalcogenides (NMCs) as alternative PSs, and study their high-energy transfer efficiency, rational designs, and potential applications in cancer-targeted PDT. We discuss the latest advancements in treating the correlation of the self-aggregation of NMCs with their passive tumor cell targeting, and highlight their ability to efficiently produce ROSs. Treatment of deep-seated tumors by using these PSs upon preferential uptake by tumor tissues due to the enhanced permeability and retention effect, is also reviewed. We finally summarize the main future perspectives of NMCs as next-generation PSs within the context of cancer theranostics.

Title: Particle Size Dependent Photodynamic Anticancer Activities of Multifunctional Magnetic Submicron Particles in Prostate Cancer
Authors: Kyong-Hoon Choi, Ki Chang Nam, Leszek Malkinski, Eun Ha Choi, Jin-Seung Jung, and Bong Joo Park
Affiliation: Kwangwoon University, Korea
Abstract: In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe2O4-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as photodynamic therapeutic agents in cancer cells. In order to provide selective targeting of cancer cells and destruction of cancer cell functionality, the basic cobalt ferrite (CoFe2O4) particles were covalently bonded with hematoporphyrin (HP) and folic acid (FA) molecules. The magnetic properties of the CoFe2O4 particles were finely adjusted by controlling the size of the primary CoFe2O4 nanograins and the secondary superstructure composited particles formed by aggregation of the nanograins. The prepared CoFe2O4-HPs-FAs exhibited high water solubility, good MRI capacity, and biocompatibility without any cytotoxicity in vitro. In particular, our CoFe2O4-HPs-FAs exhibited remarkable photodynamic anticancer efficiency via induction of apoptotic cell death in PC-3 prostate cancer cells in a particle size- and concentration-dependent manner. This size-dependent effect was determined by the specific surface area of each particle because the number of HP molecules increased with decreasing size and increasing surface area. These results indicated that our CoFe2O4-HPs-FAs may be applicable for photodynamic therapy (PDT) and may have tremendous potential as a therapeutic agent for MRI-based PDT owing to their high saturation value of magnetization and superparamagnetism.

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