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Photodynamic Therapy in Cancer Treatment 2021
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Photodynamic Therapy in Cancer Treatment 2021

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

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 34356

Special Issue Editors

Dr. Carlos Monteiro

E-Mail Website
Guest Editor
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Interests: organic synthesis; fine chemistry; medicinal chemistry; pharmaceutical chemistry; drug development; porphyrin; photochemistry; photodynamic therapy; antimicrobial; ceramic materials; decarbonization; synthetic fuels
Special Issues, Collections and Topics in MDPI journals
Dr. Catarina I. V. Ramos

E-Mail Website
Guest Editor
Department of Chemistry and LAQV-REQUIMTE, University of Aveiro, 3810-193 Aveiro, Portugal
Interests: photodynamic therapy of cancer; drug development; water-soluble tetrapyrrolic macrocycles for biomedical applications; photodynamic therapy; G-quadruplex–porphyrinoid interactions; cancer cells proliferation control
Special Issues, Collections and Topics in MDPI journals
Dr. M. Amparo F. Faustino

E-Mail Website
Guest Editor
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Interests: porphyrin derivatives and analogues; cyclo-addition reactions; photodynamic applications; DSSC cells; antimicrobials; antitumoral
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Photodynamic therapy (PDT) is a clinically approved treatment for oncologic and non-oncologic diseases based on the interaction of a photosensitizing dye (PS), light and dioxygen. Through this interaction, cytotoxic reactive oxygen species (ROS) are produced, which trigger a cascade of reactions that lead to the destruction of tumor cells and tumor vasculature, making PDT an effective anticancer procedure. The main advantages of PDT compared with traditional oncological therapies are due to its relatively non-invasive nature, lower systemic toxicity, relatively selective destruction of undesired cells, good cosmetic outcome and its ability to stimulate the immune system, as well as its good tolerability profile. However, PDT has also some limitations, and thus there is significant room for improvement, especially in the search for new and more efficient PS. Better PS should be rationally designed and prepared to match, as closely as possible, the properties that define the profile of the ideal PS.

Following the success of the 2020 Special Issue of “Photodynamic Therapy in Cancer Treatment” with the present edition, we are opening a forum for the presentation of the newest, most exciting results and perspectives in the PDT research field, namely, new photosensitizers, photochemical and photobiological aspects, targeting, and biological applications. We invite original research papers and comprehensive reviews covering any aspect related to the abovementioned topics. 

Dr. Carlos J. P. Monteiro
Dr. Catarina I. V. Ramos
Dr. M. Amparo F. Faustino
Guest Editors

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Keywords

  • photodynamic therapy
  • photosensitizers
  • porphyrins
  • phthalocyanines
  • BODIPY
  • drug delivery systems
  • tumors
  • nanoparticles
  • liposomes
  • photochemical properties
  • photophysical properties
  • photobiological properties
  • immune system
  • mechanism of action

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Published Papers (9 papers)

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Research

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20 pages, 3776 KiB  
Article
Immunomodulatory Effects by Photodynamic Treatment of Glioblastoma Cells In Vitro
by Friederike Rothe, Ina Patties, Rolf-Dieter Kortmann and Annegret Glasow
Molecules 2022, 27(11), 3384; https://doi.org/10.3390/molecules27113384 - 24 May 2022
Cited by 3 | Viewed by 2070
Abstract
Multimodal treatment adding immunotherapy and photodynamic treatment (PDT) to standard therapy might improve the devastating therapeutic outcome of glioblastoma multiforme patients. As a first step, we provide investigations to optimize dendritic cell (DC) vaccination by using PDT and ionizing radiation (IR) to achieve [...] Read more.
Multimodal treatment adding immunotherapy and photodynamic treatment (PDT) to standard therapy might improve the devastating therapeutic outcome of glioblastoma multiforme patients. As a first step, we provide investigations to optimize dendritic cell (DC) vaccination by using PDT and ionizing radiation (IR) to achieve maximal synergistic effects. In vitro experiments were conducted on murine glioblastoma GL261 cells, primary DCs differentiated from bone marrow and T cells, isolated from the spleen. Induction of cell death, reactive oxygen species, and inhibition of proliferation by tetrahydroporphyrin-tetratosylat (THPTS)-PDT and IR were confirmed by WST-1, LDH, ROS, and BrdU assay. Tumor cargo (lysate or cells) for DC load was treated with different combinations of THPTS-PDT, freeze/thaw cycles, and IR and immunogenicity analyzed by induction of T-cell activation. Cellular markers (CD11c, 83, 86, 40, 44, 69, 3, 4, 8, PD-L1) were quantified by flow cytometry. Cytotoxic T-cell response was evaluated by calcein AM assay. Immunogenicity of THPTS-PDT-treated GL261 cells lysate was superior to IR-treated lysate, or treated whole cells proven by increased DC phagocytosis, T-cell adhesion, proliferation, cytolytic activity, and cytokine release. These data strongly support the application of PDT together with IR for optimal immunogenic cell death induction in tumor cell lysate used to pulse DC vaccines. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment 2021)
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10 pages, 4585 KiB  
Article
Near-Infrared Light Irradiation of Porphyrin-Modified Gold Nanoparticles Promotes Cancer-Cell-Specific Cytotoxicity
by Hiromi Kurokawa, Atsushi Taninaka, Toru Yoshitomi, Hidemi Shigekawa and Hirofumi Matsui
Molecules 2022, 27(4), 1238; https://doi.org/10.3390/molecules27041238 - 12 Feb 2022
Cited by 8 | Viewed by 2579
Abstract
The use of nanoparticles has been investigated as a new cancer treatment. These can induce specific cytotoxicity in cancer cells. In particular, Au nanoparticles (AuNPs) have unique characteristics. The maximum absorption spectrum of AuNPs can be adjusted to modify their size or shape [...] Read more.
The use of nanoparticles has been investigated as a new cancer treatment. These can induce specific cytotoxicity in cancer cells. In particular, Au nanoparticles (AuNPs) have unique characteristics. The maximum absorption spectrum of AuNPs can be adjusted to modify their size or shape to absorb near-infrared light that can penetrate into tissue without photodamage. Thus, the combination of AuNPs and near-infrared light can be used to treat cancer in deep-seated organs. To obtain effective cancer-specific accumulation of AuNPs, we focused on porphyrin and synthesized a porphyrin-attached Au compound: Au-HpD. In this study, we investigated whether Au-HpD possesses cancer-specific accumulation and cytotoxicity. Intracellular Au-HpD accumulation was higher in cancer cells than in normal cells. In order to analyze the cytotoxicity induced by Au-HpD, cancer cells and normal cells were co-cultured in the presence of Au-HpD; then, they were subjected to 870 nm laser irradiation. We observed that, after laser irradiation, cancer cells showed significant morphological changes, such as chromatin condensation and nuclear fragmentation indicative of cell apoptosis. This strong effect was not observed when normal cells were irradiated. Moreover, cancer cells underwent cell apoptosis with combination therapy. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment 2021)
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13 pages, 2362 KiB  
Article
Response of MCF-7 Breast Cancer Cells Overexpressed with P-Glycoprotein to Apoptotic Induction after Photodynamic Therapy
by Eric Chekwube Aniogo, Blassan P. George and Heidi Abrahamse
Molecules 2021, 26(23), 7412; https://doi.org/10.3390/molecules26237412 - 6 Dec 2021
Cited by 4 | Viewed by 3446
Abstract
Multidrug resistance (MDR) has posed a significant threat to cancer treatment and has led to the emergence of a new therapeutic regime of photodynamic therapy (PDT) to curb the menace. The PDT modality employs a photosensitiser (PS), excited at a specific wavelength of [...] Read more.
Multidrug resistance (MDR) has posed a significant threat to cancer treatment and has led to the emergence of a new therapeutic regime of photodynamic therapy (PDT) to curb the menace. The PDT modality employs a photosensitiser (PS), excited at a specific wavelength of light to kill cancer cells. In the present study, we used a zinc phthalocyanine tetrasulfonic acid PS to mediate the photodynamic killing of MCF-7 cells overexpressed with P-glycoprotein (P-gp) and investigate the response to cell death induction. After photodynamic treatment, MCF-7 cells undergo cell death, and indicators like Annexin V/PI staining, DNA fragmentation, and measurement of apoptotic protein expression were investigated. Results showed increased externalisation of phosphatidylserine protein, measured as a percentage in flow cytometry indicative of apoptotic induction. This expression was significant (p < 0.006) for the untreated control cells, and there was no detection of DNA fragments after a laser fluence of 20 J/cm2. In addition, a statistically significant difference (p < 0.05) was seen in caspase 8 activity and Bax protein expression. These findings were indicative of apoptotic induction and thus seem to represent the extrinsic apoptotic pathway. This study shows the role of PDT in the treatment of a resistant phenotype breast cancer. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment 2021)
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14 pages, 4011 KiB  
Article
The First Selenoanhydride in the Series of Chlorophyll a Derivatives, Its Stability and Photoinduced Cytotoxicity
by Viktor Pogorilyy, Anna Plyutinskaya, Nikita Suvorov, Ekaterina Diachkova, Yuriy Vasil’ev, Andrei Pankratov, Andrey Mironov and Mikhail Grin
Molecules 2021, 26(23), 7298; https://doi.org/10.3390/molecules26237298 - 1 Dec 2021
Cited by 2 | Viewed by 2145
Abstract
In this work, we obtained the first selenium-containing chlorin with a chalcogen atom in exlocycle E. It was shown that the spectral properties were preserved in the target compound and the stability increased at two different pH values, in comparison with the starting [...] Read more.
In this work, we obtained the first selenium-containing chlorin with a chalcogen atom in exlocycle E. It was shown that the spectral properties were preserved in the target compound and the stability increased at two different pH values, in comparison with the starting purpurin-18. The derivatives have sufficiently high fluorescence and singlet oxygen quantum yields. The photoinduced cytotoxicity of sulfur- and selenium-anhydrides of chlorin p6 studied for the first time in vitro on the S37 cell line was found to be two times higher that of purpurin-18 and purpurinimide studied previously. Moreover, the dark cytotoxicity increased four-fold in comparison with the latter compounds. Apparently, the increase in the dark cytotoxicity is due to the interaction of the pigments studied with sulfur- and selenium-containing endogenous intracellular compounds. Intracellular distributions of thioanhydride and selenoanhydride chlorin p6 in S37 cells were shown in cytoplasm by diffusion distribution. The intracellular concentration of the sulfur derivative turned out to be higher and, as a consequence, its photoinduced cytotoxicity was higher as well. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment 2021)
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15 pages, 4235 KiB  
Article
Photodynamic Therapy with Zinc Phthalocyanine Inhibits the Stemness and Development of Colorectal Cancer: Time to Overcome the Challenging Barriers?
by Mahsa Gholizadeh, Mohammad Amin Doustvandi, Fateme Mohammadnejad, Mahdi Abdoli Shadbad, Habib Tajalli, Oronzo Brunetti, Antonella Argentiero, Nicola Silvestris and Behzad Baradaran
Molecules 2021, 26(22), 6877; https://doi.org/10.3390/molecules26226877 - 15 Nov 2021
Cited by 9 | Viewed by 2425
Abstract
Photodynamic therapy (PDT) is a light-based cancer therapy approach that has shown promising results in treating various malignancies. Growing evidence indicates that cancer stem cells (CSCs) are implicated in tumor recurrence, metastasis, and cancer therapy resistance in colorectal cancer (CRC); thus, targeting these [...] Read more.
Photodynamic therapy (PDT) is a light-based cancer therapy approach that has shown promising results in treating various malignancies. Growing evidence indicates that cancer stem cells (CSCs) are implicated in tumor recurrence, metastasis, and cancer therapy resistance in colorectal cancer (CRC); thus, targeting these cells can ameliorate the prognosis of affected patients. Based on our bioinformatics results, SOX2 overexpression is significantly associated with inferior disease-specific survival and worsened the progression-free interval of CRC patients. Our results demonstrate that zinc phthalocyanine (ZnPc)-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially decrease tumor migration via downregulating MMP9 and ROCK1 and inhibit the clonogenicity of SW480 cells via downregulating CD44 and SOX2. Despite inhibiting clonogenicity, ZnPc-PDT with 12 J/cm2 irradiation fails to downregulate CD44 expression in SW480 cells. Our results indicate that ZnPc-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially reduce the cell viability of SW480 cells and stimulate autophagy in the tumoral cells. Moreover, our results show that ZnPc-PDT with 12 J/cm2 or 24 J/cm2 irradiation can substantially arrest the cell cycle at the sub-G1 level, stimulate the intrinsic apoptosis pathway via upregulating caspase-3 and caspase-9 and downregulating Bcl-2. Indeed, our bioinformatics results show considerable interactions between the studied CSC-related genes with the studied migration- and apoptosis-related genes. Collectively, the current study highlights the potential role of ZnPc-PDT in inhibiting stemness and CRC development, which can ameliorate the prognosis of CRC patients. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment 2021)
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Review

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21 pages, 8372 KiB  
Review
Porphyrin NanoMetal-Organic Frameworks as Cancer Theranostic Agents
by Flávio Figueira, João P. C. Tomé and Filipe A. Almeida Paz
Molecules 2022, 27(10), 3111; https://doi.org/10.3390/molecules27103111 - 12 May 2022
Cited by 11 | Viewed by 2671
Abstract
Metal-Organic Frameworks (MOFs) are hybrid multifunctional platforms that have found remarkable applications in cancer treatment and diagnostics. Independently, these materials can be employed in cancer treatment as intelligent drug carriers in chemotherapy, photothermal therapy, and photodynamic therapy; conversely, MOFs can further be used [...] Read more.
Metal-Organic Frameworks (MOFs) are hybrid multifunctional platforms that have found remarkable applications in cancer treatment and diagnostics. Independently, these materials can be employed in cancer treatment as intelligent drug carriers in chemotherapy, photothermal therapy, and photodynamic therapy; conversely, MOFs can further be used as diagnostic tools in fluorescence imaging, magnetic resonance imaging, computed tomography imaging, and photoacoustic imaging. One essential property of these materials is their great ability to fine-tune their composition toward a specific application by way of a judicious choice of the starting building materials (metal nodes and organic ligands). Moreover, many advancements were made concerning the preparation of these materials, including the ability to downsize the crystallites yielding nanoporous porphyrin MOFs (NMOFs) which are of great interest for clinical treatment and diagnostic theranostic tools. The usage of porphyrins as ligands allows a high degree of multifunctionality. Historically these molecules are well known for their reactive oxygen species formation and strong fluorescence characteristics, and both have proved helpful in cancer treatment and diagnostic tools. The anticipation that porphyrins in MOFs could prompt the resulting materials to multifunctional theranostic platforms is a reality nowadays with a series of remarkable and ground-breaking reports available in the literature. This is particularly remarkable in the last five years, when the scientific community witnessed rapid development in porphyrin MOFs theranostic agents through the development of imaging technologies and treatment strategies for cancer. This manuscript reviews the most relevant recent results and achievements in this particular area of interest in MOF chemistry and application. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment 2021)
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28 pages, 6459 KiB  
Review
Porphyrin/Chlorin Derivatives as Promising Molecules for Therapy of Colorectal Cancer
by Fatima Dandash, David Y. Leger, Mona Diab-Assaf, Vincent Sol and Bertrand Liagre
Molecules 2021, 26(23), 7268; https://doi.org/10.3390/molecules26237268 - 30 Nov 2021
Cited by 20 | Viewed by 3457
Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related death. The demand for new therapeutic approaches has increased attention paid toward therapies with high targeting efficiency, improved selectivity and few side effects. Porphyrins are powerful molecules with exceptional properties and multifunctional uses, and [...] Read more.
Colorectal cancer (CRC) is a leading cause of cancer-related death. The demand for new therapeutic approaches has increased attention paid toward therapies with high targeting efficiency, improved selectivity and few side effects. Porphyrins are powerful molecules with exceptional properties and multifunctional uses, and their special affinity to cancer cells makes them the ligands par excellence for anticancer drugs. Porphyrin derivatives are used as the most important photosensitizers (PSs) for photodynamic therapy (PDT), which is a promising approach for anticancer treatment. Nevertheless, the lack of solubility and selectivity of the large majority of these macrocycles led to the development of different photosensitizer complexes. In addition, targeting agents or nanoparticles were used to increase the efficiency of these macrocycles for PDT applications. On the other hand, gold tetrapyrrolic macrocycles alone showed very interesting chemotherapeutic activity without PDT. In this review, we discuss the most important porphyrin derivatives, alone or associated with other drugs, which have been found effective against CRC, as we describe their modifications and developments through substitutions and delivery systems. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment 2021)
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39 pages, 9353 KiB  
Review
Prospects for More Efficient Multi-Photon Absorption Photosensitizers Exhibiting Both Reactive Oxygen Species Generation and Luminescence
by Emma Robbins, Stéphanie Leroy-Lhez, Nicolas Villandier, Marek Samoć and Katarzyna Matczyszyn
Molecules 2021, 26(20), 6323; https://doi.org/10.3390/molecules26206323 - 19 Oct 2021
Cited by 13 | Viewed by 4386
Abstract
The use of two-photon absorption (TPA) for such applications as microscopy, imaging, and photodynamic therapy (PDT) offers several advantages over the usual one-photon excitation. This creates a need for photosensitizers that exhibit both strong two-photon absorption and the highly efficient generation of reactive [...] Read more.
The use of two-photon absorption (TPA) for such applications as microscopy, imaging, and photodynamic therapy (PDT) offers several advantages over the usual one-photon excitation. This creates a need for photosensitizers that exhibit both strong two-photon absorption and the highly efficient generation of reactive oxygen species (ROS), as well as, ideally, bright luminescence. This review focuses on different strategies utilized to improve the TPA properties of various multi-photon absorbing species that have the required photophysical properties. Along with well-known families of photosensitizers, including porphyrins, we also describe other promising organic and organometallic structures and more complex systems involving organic and inorganic nanoparticles. We concentrate on the published studies that provide two-photon absorption cross-section values and the singlet oxygen (or other ROS) and luminescence quantum yields, which are crucial for potential use within PDT and diagnostics. We hope that this review will aid in the design and modification of novel TPA photosensitizers, which can help in exploiting the features of nonlinear absorption processes. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment 2021)
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26 pages, 4470 KiB  
Review
Molecular Targeting of Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR)
by Nichole E. M. Kaufman, Simran Dhingra, Seetharama D. Jois and Maria da Graça H. Vicente
Molecules 2021, 26(4), 1076; https://doi.org/10.3390/molecules26041076 - 18 Feb 2021
Cited by 61 | Viewed by 9566
Abstract
Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are two extensively studied membrane-bound receptor tyrosine kinase proteins that are frequently overexpressed in many cancers. As a result, these receptor families constitute attractive targets for imaging and therapeutic applications in [...] Read more.
Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are two extensively studied membrane-bound receptor tyrosine kinase proteins that are frequently overexpressed in many cancers. As a result, these receptor families constitute attractive targets for imaging and therapeutic applications in the detection and treatment of cancer. This review explores the dynamic structure and structure-function relationships of these two growth factor receptors and their significance as it relates to theranostics of cancer, followed by some of the common inhibition modalities frequently employed to target EGFR and VEGFR, such as tyrosine kinase inhibitors (TKIs), antibodies, nanobodies, and peptides. A summary of the recent advances in molecular imaging techniques, including positron emission tomography (PET), single-photon emission computerized tomography (SPECT), computed tomography (CT), magnetic resonance imaging (MRI), and optical imaging (OI), and in particular, near-IR fluorescence imaging using tetrapyrrolic-based fluorophores, concludes this review. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment 2021)
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