Editorial

3 pages, 161 KiB

Open AccessEditorial

Introduction to “Advances in Photodynamic Therapy 2018”

by Michael R Hamblin

Molecules 2019, 24(1), 160; https://doi.org/10.3390/molecules24010160 - 03 Jan 2019

Cited by 1 | Viewed by 2754

This Special Issue of Molecules entitled “Advances in Photodynamic Therapy 2018” contains seven papers, including five original reports and two reviews. [...] Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy 2018)

Research

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14 pages, 2579 KiB

Open AccessFeature PaperArticle

Selective Photokilling of Human Pancreatic Cancer Cells Using Cetuximab-Targeted Mesoporous Silica Nanoparticles for Delivery of Zinc Phthalocyanine

by Özge Er, Suleyman Gokhan Colak, Kasim Ocakoglu, Mine Ince, Roger Bresolí-Obach, Margarita Mora, Maria Lluïsa Sagristá, Fatma Yurt and Santi Nonell

Molecules 2018, 23(11), 2749; https://doi.org/10.3390/molecules23112749 - 24 Oct 2018

Cited by 32 | Viewed by 4128

Abstract

Background: Photodynamic therapy (PDT) is a non-invasive and innovative cancer therapy based on the photodynamic effect. In this study, we sought to determine the singlet oxygen production, intracellular uptake, and in vitro photodynamic therapy potential of Cetixumab-targeted, zinc(II) 2,3,9,10,16,17,23,24-octa(tert-butylphenoxy))phthalocyaninato(2-)-N²⁹,N³⁰,N [...] Read more.

Background: Photodynamic therapy (PDT) is a non-invasive and innovative cancer therapy based on the photodynamic effect. In this study, we sought to determine the singlet oxygen production, intracellular uptake, and in vitro photodynamic therapy potential of Cetixumab-targeted, zinc(II) 2,3,9,10,16,17,23,24-octa(tert-butylphenoxy))phthalocyaninato(2-)-N²⁹,N³⁰,N³¹,N³² (ZnPcOBP)-loaded mesoporous silica nanoparticles against pancreatic cancer cells. Results: The quantum yield (Φ_Δ) value of ZnPcOBP was found to be 0.60 in toluene. In vitro cellular studies were performed to determine the dark- and phototoxicity of samples with various concentrations of ZnPcOBP by using pancreatic cells (AsPC-1, PANC-1 and MIA PaCa-2) and 20, 30, and 40 J/cm² light fluences. No dark toxicity was observed for any sample in any cell line. ZnPcOBP alone showed a modest photodynamic activity. However, when incorporated in silica nanoparticles, it showed a relatively high phototoxic effect, which was further enhanced by Cetuximab, a monoclonal antibody that targets the Epidermal Growth Factor Receptor (EGFR). The cell-line dependent photokilling observed correlates well with EGFR expression levels in these cells. Conclusions: Imidazole-capped Cetuximab-targeted mesoporous silica nanoparticles are excellent vehicles for the selective delivery of ZnPcOBP to pancreatic cancer cells expressing the EGFR receptor. The novel nanosystem appears to be a suitable agent for photodynamic therapy of pancreatic tumors. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy 2018)

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12 pages, 3077 KiB

Open AccessFeature PaperArticle

Measurement of Cyanine Dye Photobleaching in Photosensitizer Cyanine Dye Conjugates Could Help in Optimizing Light Dosimetry for Improved Photodynamic Therapy of Cancer

by Nadine S. James, Ravindra R. Cheruku, Joseph R. Missert, Ulas Sunar and Ravindra K. Pandey

Molecules 2018, 23(8), 1842; https://doi.org/10.3390/molecules23081842 - 24 Jul 2018

Cited by 46 | Viewed by 5961

Abstract

Photodynamic therapy (PDT) of cancer is dependent on three primary components: photosensitizer (PS), light and oxygen. Because these components are interdependent and vary during the dynamic process of PDT, assessing PDT efficacy may not be trivial. Therefore, it has become necessary to develop [...] Read more.

Photodynamic therapy (PDT) of cancer is dependent on three primary components: photosensitizer (PS), light and oxygen. Because these components are interdependent and vary during the dynamic process of PDT, assessing PDT efficacy may not be trivial. Therefore, it has become necessary to develop pre-treatment planning, on-line monitoring and dosimetry strategies during PDT, which become more critical for two or more chromophore systems, for example, PS-CD (Photosensitizer-Cyanine dye) conjugates developed in our laboratory for fluorescence-imaging and PDT of cancer. In this study, we observed a significant impact of variable light dosimetry; (i) high light fluence and fluence rate (light dose: 135 J/cm², fluence rate: 75 mW/cm²) and (ii) low light fluence and fluence rate (128 J/cm² and 14 mW/cm² and 128 J/cm² and 7 mW/cm²) in photobleaching of the individual chromophores of PS-CD conjugates and their long-term tumor response. The fluorescence at the near-infrared (NIR) region of the PS-NIR fluorophore conjugate was assessed intermittently via fluorescence imaging. The loss of fluorescence, photobleaching, caused by singlet oxygen from the PS was mapped continuously during PDT. The tumor responses (BALB/c mice bearing Colon26 tumors) were assessed after PDT by measuring tumor sizes daily. Our results showed distinctive photobleaching kinetics rates between the PS and CD. Interestingly, compared to higher light fluence, the tumors exposed at low light fluence showed reduced photobleaching and enhanced long-term PDT efficacy. The presence of NIR fluorophore in PS-CD conjugates provides an opportunity of fluorescence imaging and monitoring the photobleaching rate of the CD moiety for large and deeply seated tumors and assessing PDT tumor response in real-time. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy 2018)

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17 pages, 2869 KiB

Open AccessArticle

Effects of Blue-Light-Induced Free Radical Formation from Catechin Hydrate on the Inactivation of Acinetobacter baumannii, Including a Carbapenem-Resistant Strain

by Meei-Ju Yang, Yi-An Hung, Tak-Wah Wong, Nan-Yao Lee, Jeu-Ming P. Yuann, Shiuh-Tsuen Huang, Chun-Yi Wu, Iou-Zen Chen and Ji-Yuan Liang

Molecules 2018, 23(7), 1631; https://doi.org/10.3390/molecules23071631 - 04 Jul 2018

Cited by 18 | Viewed by 4349

Abstract

Catechin is a flavan-3-ol, a derivative of flavans, with four phenolic hydroxyl groups, which exhibits a wide range of physiological properties. Chromatographic analyses were employed to examine the effects of blue light irradiation on the changes of catechin hydrate in an alkaline condition. [...] Read more.

Catechin is a flavan-3-ol, a derivative of flavans, with four phenolic hydroxyl groups, which exhibits a wide range of physiological properties. Chromatographic analyses were employed to examine the effects of blue light irradiation on the changes of catechin hydrate in an alkaline condition. In particular, the detection of a superoxide anion radical (O₂•⁻), a reactive oxygen species (ROS), and the inactivation of Acinetobacter baumannii (A. baumannii)—including a carbapenem-resistant A. baumannii (CRAB)—was investigated during the photoreaction of catechin hydrate. Following basification with blue light irradiation, the transparent solution of catechin hydrate turned yellowish, and a chromogenic catechin dimer was separated and identified as a proanthocyanidin. Adding ascorbic acid during the photolytic treatment of catechin hydrate decreased the dimer formation, suggesting that ascorbic acid can suppress the photosensitive oxidation of catechin. When catechin hydrate was irradiated by blue light in an alkaline solution, O₂•⁻ was produced via photosensitized oxidation, enhancing the inactivation of A. baumannii and CRAB. The present findings on the photon-induced oxidation of catechin hydrate provides a safe practice for the inactivation of environmental microorganisms. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy 2018)

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13 pages, 2239 KiB

Open AccessArticle

Synthesis and Evaluation of New Potential Benzo[a]phenoxazinium Photosensitizers for Anticancer Photodynamic Therapy

by Juan Zhang, Wellington Tavares de Sousa Júnior, Victor Carlos Mello da Silva, Mosar Correa Rodrigues, José Athayde Vasconcelos Morais, Jia-Li Song, Zhi-Qiang Cheng, João Paulo Figueiró Longo, Ricardo Bentes Azevedo, Cheng-Shi Jiang, Luís Alexandre Muehlmann and Hua Zhang

Molecules 2018, 23(6), 1436; https://doi.org/10.3390/molecules23061436 - 13 Jun 2018

Cited by 10 | Viewed by 4533

Abstract

The use of photodynamic therapy (PDT) and development of novel photosensitizers (PSs) for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity [...] Read more.

The use of photodynamic therapy (PDT) and development of novel photosensitizers (PSs) for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity for the first time. They are red light absorbers and show low fluorescence quantum yield. Of these compounds, PS4 exhibited a higher quantum yield for reactive oxygen species (ROS) generation. The assays with cells in vitro showed that PS1 and PS4 were not significantly toxic in the dark, but was robustly toxic against the murine breast adenocarcinoma cells 4T1 and normal murine fibroblast cells NIH-3T3 upon photoactivation. More interestingly, PS5 was particularly selective towards 4T1 cancer cells and nearly non-phototoxic to non-cancerous NIH-3T3 cells. The results described in this report suggest that these new benzo[a]phenoxazinium derivatives are potential candidates as PSs for anticancer PDT. Further investigation of benzo[a]phenoxaziniums for anticancer PDT is warranted. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy 2018)

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12 pages, 7752 KiB

Open AccessFeature PaperArticle

Assessing Photosensitizer Targeting Using Meso-Tetra(Carboxyphenyl) Porphyrin

by Upendra Chitgupi, Jonathan F. Lovell and Venugopal Rajendiran

Molecules 2018, 23(4), 892; https://doi.org/10.3390/molecules23040892 - 12 Apr 2018

Cited by 6 | Viewed by 4503

Abstract

Mesotetra(4-carboxyphenyl)porphyrin (mTCPP) is a commercially available small molecule fluorophore and photosensitizer with four free carboxylic acid groups. mTCPP can readily be conjugated with amines for facile attachment of functional groups. In this work, we synthesized and assessed tetravalent, lysine-conjugated mTCPP, for its potential [...] Read more.

Mesotetra(4-carboxyphenyl)porphyrin (mTCPP) is a commercially available small molecule fluorophore and photosensitizer with four free carboxylic acid groups. mTCPP can readily be conjugated with amines for facile attachment of functional groups. In this work, we synthesized and assessed tetravalent, lysine-conjugated mTCPP, for its potential applications in targeted imaging and photodynamic therapy. Fmoc-protected d-lysine or l-lysine was conjugated to mTCPP via amide coupling with the epsilon amine group of lysine, followed by Fmoc deprotection. The resulting compounds did not dissolve well in aqueous solvent, but could be solubilized with the assistance of surfactants, including cholic acid. The l-amino acid transporter (LAT1) can uptake diverse neutral l-amino acids. In vitro studies with U87 cells revealed a non-specific uptake of the hydrophobic Fmoc-protected lysine-conjugated mTCPP precursors, but not d- or l-lysine mTCPP. Likewise, only the Fmoc-protected compounds induced substantial phototoxicty in cells following incubation and irradiation with blue light. These experimental results do not provide evidence to suggest that lysine-mTCPP is able to specifically target cancer cells. However, they do highlight mTCPP as a convenient and accessible framework for assessing molecular targeting of photosensitizers. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy 2018)

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Review

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18 pages, 6108 KiB

Open AccessReview

Inorganic Salts and Antimicrobial Photodynamic Therapy: Mechanistic Conundrums?

by Michael R. Hamblin and Heidi Abrahamse

Molecules 2018, 23(12), 3190; https://doi.org/10.3390/molecules23123190 - 03 Dec 2018

Cited by 49 | Viewed by 6884

Abstract

We have recently discovered that the photodynamic action of many different photosensitizers (PSs) can be dramatically potentiated by addition of a solution containing a range of different inorganic salts. Most of these studies have centered around antimicrobial photodynamic inactivation that kills Gram-negative and [...] Read more.

We have recently discovered that the photodynamic action of many different photosensitizers (PSs) can be dramatically potentiated by addition of a solution containing a range of different inorganic salts. Most of these studies have centered around antimicrobial photodynamic inactivation that kills Gram-negative and Gram-positive bacteria in suspension. Addition of non-toxic water-soluble salts during illumination can kill up to six additional logs of bacterial cells (one million-fold improvement). The PSs investigated range from those that undergo mainly Type I photochemical mechanisms (electron transfer to produce superoxide, hydrogen peroxide, and hydroxyl radicals), such as phenothiazinium dyes, fullerenes, and titanium dioxide, to those that are mainly Type II (energy transfer to produce singlet oxygen), such as porphyrins, and Rose Bengal. At one extreme of the salts is sodium azide, that quenches singlet oxygen but can produce azide radicals (presumed to be highly reactive) via electron transfer from photoexcited phenothiazinium dyes. Potassium iodide is oxidized to molecular iodine by both Type I and Type II PSs, but may also form reactive iodine species. Potassium bromide is oxidized to hypobromite, but only by titanium dioxide photocatalysis (Type I). Potassium thiocyanate appears to require a mixture of Type I and Type II photochemistry to first produce sulfite, that can then form the sulfur trioxide radical anion. Potassium selenocyanate can react with either Type I or Type II (or indeed with other oxidizing agents) to produce the semi-stable selenocyanogen (SCN)₂. Finally, sodium nitrite may react with either Type I or Type II PSs to produce peroxynitrate (again, semi-stable) that can kill bacteria and nitrate tyrosine. Many of these salts (except azide) are non-toxic, and may be clinically applicable. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy 2018)

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69 pages, 23473 KiB

Open AccessFeature PaperReview

Use of Cyclodextrins in Anticancer Photodynamic Therapy Treatment

by Amina Ben Mihoub, Ludivine Larue, Albert Moussaron, Zahraa Youssef, Ludovic Colombeau, Francis Baros, Céline Frochot, Régis Vanderesse and Samir Acherar

Molecules 2018, 23(8), 1936; https://doi.org/10.3390/molecules23081936 - 02 Aug 2018

Cited by 40 | Viewed by 8578

Abstract

Photodynamic therapy (PDT) is mainly used to destroy cancerous cells; it combines the action of three components: a photoactivatable molecule or photosensitizer (PS), the light of an appropriate wavelength, and naturally occurring molecular oxygen. After light excitation of the PS, the excited PS [...] Read more.

Photodynamic therapy (PDT) is mainly used to destroy cancerous cells; it combines the action of three components: a photoactivatable molecule or photosensitizer (PS), the light of an appropriate wavelength, and naturally occurring molecular oxygen. After light excitation of the PS, the excited PS then reacts with molecular oxygen to produce reactive oxygen species (ROS), leading to cellular damage. One of the drawbacks of PSs is their lack of solubility in water and body tissue fluids, thereby causing low bioavailability, drug-delivery efficiency, therapeutic efficacy, and ROS production. To improve the water-solubility and/or drug delivery of PSs, using cyclodextrins (CDs) is an interesting strategy. This review describes the in vitro or/and in vivo use of natural and derived CDs to improve antitumoral PDT efficiency in aqueous media. To achieve these goals, three types of binding modes of PSs with CDs are developed: non-covalent CD–PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies. This review is divided into three parts: (1) non-covalent CD-PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies, (2) incorporating CD–PS systems into hybrid nanoparticles (NPs) using up-converting or other types of NPs, and (3) CDs with fullerenes as PSs. Full article

(This article belongs to the Special Issue Advances in Photodynamic Therapy 2018)

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