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Photodynamic Therapy

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

Deadline for manuscript submissions: closed (31 October 2016) | Viewed by 31267

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Prof. Dr. Norbert Lange

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

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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

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Published Papers (5 papers)

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2638 KiB

Open AccessArticle

Complexing Methylene Blue with Phosphorus Dendrimers to Increase Photodynamic Activity

by Monika Dabrzalska, Anna Janaszewska, Maria Zablocka, Serge Mignani, Jean Pierre Majoral and Barbara Klajnert-Maculewicz

Molecules 2017, 22(3), 345; https://doi.org/10.3390/molecules22030345 - 23 Feb 2017

Cited by 17 | Viewed by 5798

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, 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)

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2534 KiB

Open AccessArticle

Preclinical Study of Antineoplastic Sinoporphyrin Sodium-PDT via In Vitro and In Vivo Models

by Rui Shi, Chao Li, Zhihuan Jiang, Wanfang Li, Aiping Wang and Jinfeng Wei

Molecules 2017, 22(1), 112; https://doi.org/10.3390/molecules22010112 - 11 Jan 2017

Cited by 23 | Viewed by 5841

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 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)

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5416 KiB

Open AccessArticle

In Vitro Photodynamic Effect of Phycocyanin against Breast Cancer Cells

by Subramaniyan Bharathiraja, Hansu Seo, Panchanathan Manivasagan, Madhappan Santha Moorthy, Suhyun Park and Jungwan Oh

Molecules 2016, 21(11), 1470; https://doi.org/10.3390/molecules21111470 - 03 Nov 2016

Cited by 59 | Viewed by 8706

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 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)

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2521 KiB

Open AccessArticle

Evaluation of Hydrogel Suppositories for Delivery of 5-Aminolevulinic Acid and Hematoporphyrin Monomethyl Ether to Rectal Tumors

by Xuying Ye, Huijuan Yin, Yu Lu, Haixia Zhang and Han Wang

Molecules 2016, 21(10), 1347; https://doi.org/10.3390/molecules21101347 - 12 Oct 2016

Cited by 13 | Viewed by 5311

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 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)

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3810 KiB

Open AccessArticle

Size-Dependent Photodynamic Anticancer Activity of Biocompatible Multifunctional Magnetic Submicron Particles in Prostate Cancer Cells

by Kyong-Hoon Choi, Ki Chang Nam, Leszek Malkinski, Eun Ha Choi, Jin-Seung Jung and Bong Joo Park

Molecules 2016, 21(9), 1187; https://doi.org/10.3390/molecules21091187 - 06 Sep 2016

Cited by 16 | Viewed by 5126

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 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)

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