|
1
|
de Alencar FMS, Gouveia FS, Oliveira GDFSD, Andrade AL, Vasconcelos MAD, Ayala AP, Gondim ACS, Carvalho IMMD, Moraes CAF, Palmeira-Mello MV, Batista AA, Lopes LGDF, Sousa EHS. Terpyridine-based ruthenium complexes containing a 4,5-diazafluoren-9-one ligand with light-driven enhancement of biological activity. Dalton Trans 2025; 54:1850-1870. [PMID: 39686803 DOI: 10.1039/d4dt02562h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2024]
Abstract
There has been growing effort in the scientific community to develop new antibiotics to address the major threat of bacterial resistance. One promising approach is the use of metal complexes that provide broader opportunities. Among these systems, polypyridine-ruthenium(II) complexes have received particular attention as drug candidates. Here, we prepared two new ruthenium(II) complexes with the formulation [Ru(DFO)(phtpy-R)Cl](PF6), where phtpy = 4'-phenyl-2,2':6',2''-terpyridine; R = -H(MPD1), -CH3(MPD2); and DFO = 4,5-diazafluoren-9-one, and investigated their chemical, biochemical and antibacterial activities. These compounds exhibit photoreactivity and produce reactive oxygen species (ROSs). Photogeneration of singlet oxygen (1O2) was measured in acetonitrile with significant quantum yields using blue light, Φ = 0.40 and 0.39 for MDP1 and MPD2, respectively. Further studies have shown that MPD1 and MPD2 can generate superoxide radicals. Antibacterial assays demonstrated a significant enhancement in MIC (minimum inhibitory concentration) upon blue light irradiation (>32-fold), with MICs of 15.6 μg mL-1 (S. aureus, ATCC 700698) and 3.9 μg mL-1 (S. epidermidis, ATCC 35984) for both metal complexes. Interestingly, an MIC of 15.6 μg mL-1 for MPD1 and MPD2 was observed against S. epidermidis ATCC 12228 under red light irradiation. The latter results are encouraging, considering that red light penetrates deeper into the skin. In addition, no significant cytotoxicity was observed in some mammalian cells, even upon light irradiation, supporting their potential safety. Altogether, these data show evidence of the potential use of these compounds as antimicrobial photodynamic therapeutic agents, enriching our arsenal to combat this worldwide bacterial threat.
Collapse
Affiliation(s)
| | - Florencio Sousa Gouveia
- Group of Bioinorganic, Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza, Brazil.
| | | | - Alexandre Lopes Andrade
- Integrated Biomolecular Laboratory, Department of Pathology and Legal Medicine, Federal University of Ceara, Fortaleza, Brazil
| | | | | | - Ana Claudia Silva Gondim
- Group of Bioinorganic, Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza, Brazil.
| | | | | | - Marcos V Palmeira-Mello
- Department of Chemistry, Federal University of São Carlos, 13565-905, São Carlos, SP, Brazil
| | - Alzir Azevedo Batista
- Department of Chemistry, Federal University of São Carlos, 13565-905, São Carlos, SP, Brazil
| | - Luiz Gonzaga de França Lopes
- Group of Bioinorganic, Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza, Brazil.
| | - Eduardo Henrique Silva Sousa
- Group of Bioinorganic, Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza, Brazil.
| |
Collapse
|
|
2
|
Mušković M, Lončarić M, Ratkaj I, Malatesti N. Impact of the hydrophilic-lipophilic balance of free-base and Zn(II) tricationic pyridiniumporphyrins and irradiation wavelength in PDT against the melanoma cell lines. Eur J Med Chem 2025; 282:117063. [PMID: 39566242 DOI: 10.1016/j.ejmech.2024.117063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 11/11/2024] [Accepted: 11/13/2024] [Indexed: 11/22/2024]
Abstract
The amphiphilic and asymmetric structure of porphyrins, when used as photosensitizers (PSs) for photodynamic therapy (PDT), has been shown through numerous previous studies to be a very important property that facilitates their entry into cells, which improves their efficiency in PDT. In this work, two groups of cationic AB3 pyridiniumporphyrins, free-base and chelated with Zn(II), both substituted with alkyl chains of various lengths, were studied in PDT on melanoma cell lines. The aim was to investigate the impact of hydrophilic-lipophilic balance and Zn(II) chelation, and the importance of matching the irradiation wavelength to the optical properties of the PS on in vitro PDT efficiency. Therefore, spectroscopic studies, singlet oxygen production and lipophilicity as well as cellular uptake, localization and cytotoxicity studies of the two series of porphyrins were performed. In both series of porphyrins, the longest alkyl chain (17 C-atoms long) enables the greatest internalization of the PS. Chelation with Zn(II) resulted in better physicochemical properties, but slower cellular internalization. As expected, free-base porphyrins were more PDT efficient than their Zn(II) complexes after 30-min photoactivation by low-fluence (2 mW/cm2) red light (643 nm). However the use of orange light (606 nm) with the same fluence rate was more suitable for Zn(II) porphyrins and resulted in similar overall toxicity to their free-base analogues with similar lipophilicity. Although the highest phototoxicity was achieved with the PSs carrying the longest alkyl chain, TMPyP3-C13H27 and Zn(II)-TMPyP3-C13H27 proved to be the most promising candidates for use in PDT as they exhibit high phototoxicity, but also greater selectivity towards melanoma cell lines (MeWo and A375) compared to fibroblasts (HDF).
Collapse
Affiliation(s)
- Martina Mušković
- Faculty of Biotechnology and Drug Development, University of Rijeka, Radmile Matejčić 2, Rijeka, Croatia
| | - Martin Lončarić
- Laboratory for Photonics and Quantum Optics, Division of Experimental Physics, Ruđer Bošković Institute, Bijenička cesta 54, Zagreb, Croatia
| | - Ivana Ratkaj
- Faculty of Biotechnology and Drug Development, University of Rijeka, Radmile Matejčić 2, Rijeka, Croatia.
| | - Nela Malatesti
- Faculty of Biotechnology and Drug Development, University of Rijeka, Radmile Matejčić 2, Rijeka, Croatia.
| |
Collapse
|
|
3
|
Chaves I, Morais FMP, Vieira C, Bartolomeu M, Faustino MAF, Neves MGMS, Almeida A, Moura NMM. Can Porphyrin-Triphenylphosphonium Conjugates Enhance the Photosensitizer Performance Toward Bacterial Strains? ACS APPLIED BIO MATERIALS 2024; 7:5541-5552. [PMID: 39008849 PMCID: PMC11337165 DOI: 10.1021/acsabm.4c00659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 06/26/2024] [Accepted: 07/01/2024] [Indexed: 07/17/2024]
Abstract
Antimicrobial photodynamic treatment (aPDT) offers an alternative option for combating microbial pathogens, and in this way, addressing the challenges of growing antimicrobial resistance. In this promising and effective approach, cationic porphyrins and related macrocycles have emerged as leading photosensitizers (PS) for aPDT. In general, their preparation occurs via N-alkylation of nitrogen-based moieties with alkyl halides, which limits the ability to fine-tune the features of porphyrin-based PS. Herein, is reported that the conjugation of porphyrin macrocycles with triphenylphosphonium units created a series of effective cationic porphyrin-based PS for aPDT. The presence of positive charges at both the porphyrin macrocycle and triphenylphosphonium moieties significantly enhances the photodynamic activity of porphyrin-based PS against both Gram-positive and Gram-negative bacterial strains. Moreover, bacterial photoinactivation is achieved with a notable reduction in irradiation time, exceeding 50%, compared to 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP), used as the reference and known as good PS. The improved capability of the porphyrin macrocycle to generate singlet oxygen combined with the enhanced membrane interaction promoted by the presence of triphenylphosphonium moieties represents a promising approach to developing porphyrin-based PS with enhanced photosensitizing activity.
Collapse
Affiliation(s)
- Inês Chaves
- CESAM,
Department of Biology, University of Aveiro, Aveiro 3810-193, Portugal
| | - Filipe M. P. Morais
- LAQV-REQUIMTE,
Department of Chemistry, University of Aveiro, Aveiro 3810-193, Portugal
| | - Cátia Vieira
- CESAM,
Department of Biology, University of Aveiro, Aveiro 3810-193, Portugal
| | - Maria Bartolomeu
- CESAM,
Department of Biology, University of Aveiro, Aveiro 3810-193, Portugal
| | - M. Amparo F. Faustino
- LAQV-REQUIMTE,
Department of Chemistry, University of Aveiro, Aveiro 3810-193, Portugal
| | | | - Adelaide Almeida
- CESAM,
Department of Biology, University of Aveiro, Aveiro 3810-193, Portugal
| | - Nuno M. M. Moura
- LAQV-REQUIMTE,
Department of Chemistry, University of Aveiro, Aveiro 3810-193, Portugal
| |
Collapse
|
|
4
|
Campagno LP, Quiroga ED, Durantini EN, Alovero FL. TMPyP-mediated photoinactivation of Pseudomonas aeruginosa improved in the presence of a cationic polymer. Photochem Photobiol 2024; 100:674-685. [PMID: 37885315 DOI: 10.1111/php.13868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 09/16/2023] [Accepted: 10/06/2023] [Indexed: 10/28/2023]
Abstract
Pseudomonas aeruginosa is one of the most refractory organisms to antibiotic treatment and appears to be one of the least susceptible to photodynamic treatment. TMPyP is effective in the photoinactivation of P. aeruginosa, and the co-administration with the cationic polymer Eudragit®-E100 (Eu) potentiates this effect against isolates both sensitive and resistant to antibiotics. The fluorescent population (>98%) observed by flow cytometry after exposure to Eu + TMPyP remained unchanged after successive washings, indicating a stronger interaction/internalization of TMPyP in the bacteria, which could be attributed to the rapid neutralization of surface charges. TMPyP and Eu produced depolarization of the cytoplasmic membrane, which increased when both cationic compounds were combined. Using confocal laser scanning microscopy, heterogeneously distributed fluorescent areas were observed after TMPyP exposure, while homogeneous fluorescence and enhanced intensity were observed with Eu + TMPyP. The polymer caused alterations in the bacterial envelopes that contributed to a deeper and more homogeneous interaction/internalization of TMPyP, leading to a higher probability of damage by cytotoxic ROS and explaining the enhanced result of photodynamic inactivation. Therefore, Eu acts as an adjuvant without being by itself capable of eradicating this pathogen. Moreover, compared with other therapies, this combinatorial strategy with a polymer approved for pharmaceutical applications presents advantages in terms of toxicity risks.
Collapse
Affiliation(s)
- Luciana P Campagno
- Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba y UNITEFA-CONICET, Edificio Ciencias II, Medina Allende y Haya de la Torre, Ciudad Universitaria, Córdoba, Argentina
| | - Ezequiel D Quiroga
- Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba y UNITEFA-CONICET, Edificio Ciencias II, Medina Allende y Haya de la Torre, Ciudad Universitaria, Córdoba, Argentina
| | - Edgardo N Durantini
- IDAS-CONICET, Departamento de Química, Facultad de Ciencias Exactas, Físico-Químicas y Naturales, Universidad Nacional de Río Cuarto, Córdoba, Argentina
| | - Fabiana L Alovero
- Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba y UNITEFA-CONICET, Edificio Ciencias II, Medina Allende y Haya de la Torre, Ciudad Universitaria, Córdoba, Argentina
| |
Collapse
|
|
5
|
Rossi GG, Tisoco I, Moreira KS, de Lima Burgo TA, de Campos MMA, Iglesias BA. Photophysical, photobiological, and mycobacteria photo-inactivation properties of new meso-tetra-cationic platinum(II) metalloderivatives at meta position. Braz J Microbiol 2024; 55:11-24. [PMID: 38051456 PMCID: PMC10920514 DOI: 10.1007/s42770-023-01201-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 11/27/2023] [Indexed: 12/07/2023] Open
Abstract
In this manuscript, we report the photo-inactivation evaluation of new tetra-cationic porphyrins with peripheral Pt(II) complexes ate meta N-pyridyl positions in the antimicrobial photodynamic therapy (aPDT) of rapidly growing mycobacterial strains (RGM). Four different metalloderivatives were synthetized and applied. aPDT experiments in the strains of Mycobacteroides abscessus subsp. Abscessus (ATCC 19977), Mycolicibacterium fortuitum (ATCC 6841), Mycobacteroides abscessus subsp. Massiliense (ATCC 48898), and Mycolicibacterium smegmatis (ATCC 700084) conducted with adequate concentration of photosensitizers (PS) under white-light conditions at 90 min (irradiance of 50 mW cm-2 and a total light dosage of 270 J cm-2) showed that the Zn(II) derivative is the most effective PS significantly reduced the concentration of viable mycobacteria. The effectiveness of the molecule as PS for PDI studies is also clear with mycobacteria, which is strongly related with the porphyrin peripheral charge and coordination platinum(II) compounds and consequently about the presence of metal center ion. This class of PS may be promising antimycobacterial aPDT agents with potential applications in medical clinical cases and bioremediation.
Collapse
Affiliation(s)
- Grazielle Guidolin Rossi
- Department of Pharmaceutical Sciences, Laboratory of Mycobacteriology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
| | - Isadora Tisoco
- Department of Chemistry, Laboratory of Bioinorganic and Porphyrinic Materials, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
| | - Kelly Schneider Moreira
- Department of Chemistry, Laboratory of Bioinorganic and Porphyrinic Materials, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
- Department of Chemistry and Environmental Sciences, Ibilce, São Paulo State University (Unesp), São Jose Do Rio Preto, São Paulo State, Brazil
| | - Thiago Augusto de Lima Burgo
- Department of Chemistry and Environmental Sciences, Ibilce, São Paulo State University (Unesp), São Jose Do Rio Preto, São Paulo State, Brazil.
| | - Marli Matiko Anraku de Campos
- Department of Pharmaceutical Sciences, Laboratory of Mycobacteriology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil
| | - Bernardo Almeida Iglesias
- Department of Chemistry, Laboratory of Bioinorganic and Porphyrinic Materials, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
| |
Collapse
|
|
6
|
Belykh DV, Pylina YI, Kustov AV, Startseva OM, Belykh ES, Smirnova NL, Shukhto OV, Berezin DB. Photosensitizing effects and physicochemical properties of chlorophyll a derivatives with hydrophilic oligoethylene glycol fragments at the macrocycle periphery. Photochem Photobiol Sci 2024; 23:409-420. [PMID: 38319518 DOI: 10.1007/s43630-023-00527-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 12/19/2023] [Indexed: 02/07/2024]
Abstract
In this work, screening studies of the cytotoxic effect of chlorins with fragments of di-, tri-, and pentaethylene glycol at the macrocycle periphery in relation to HeLa, A549, and HT29 cells were performed. It is shown that, despite different hydrophobicity, all the compounds studied have a comparable photodynamic effect. The conjugate of chlorin e6 with pentaethylene glycol, which has the lowest tendency to association among the studied compounds with tropism for low density lipoproteins and the best characteristics of the formation of molecular complexes with Tween 80, has a significant difference in dark and photoinduced toxicity (ratio IC50(dark)/IC50(photo) approximately 2 orders of magnitude for all cell lines), which allows to hope for a sufficiently large "therapeutic window". A study of the interaction of this compound with HeLa cells shows that the substance penetrates the cell and, after red light irradiation induces ROS appearance inside the cell, associated, apparently, with the photogeneration of singlet oxygen. These data indicate that photoinduced toxic effects are caused by damage to intracellular structures as a result of oxidative stress. Programmed type of cell death characterized with caspase-3 induction is prevailing. So, the conjugate of chlorin e6 with pentaethylene glycol is a promising antitumor PS that can be successfully solubilized with Tween 80, which makes it suitable for further in vivo studies.
Collapse
Affiliation(s)
- D V Belykh
- Institute of Chemistry, Komi Scientific Center, Ural Branch of the Russian Academy of Sciences, 48, Pervomaiskaya St., Syktyvkar, 167982, Russia.
| | - Y I Pylina
- Institute of Biology of Komi Scientific Centre of the Ural Branch of the Russian Academy of Sciences, 28, Kommunisticheskaya St., Syktyvkar, 167982, Russian Federation
| | - A V Kustov
- G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences (ISC RAS), 1, Akademicheskaya St., 153045, Ivanovo, Russian Federation
| | - O M Startseva
- Pitirim Sorokin Syktyvkar State University, 55, Oktyabrskiy Pr., Syktyvkar, 167001, Russian Federation
| | - E S Belykh
- Institute of Biology of Komi Scientific Centre of the Ural Branch of the Russian Academy of Sciences, 28, Kommunisticheskaya St., Syktyvkar, 167982, Russian Federation
| | - N L Smirnova
- G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences (ISC RAS), 1, Akademicheskaya St., 153045, Ivanovo, Russian Federation
| | - O V Shukhto
- Institute of Macroheterocyclic Compounds, Ivanovo State University of Chemistry and Technology (ISUCT), 7, Sheremetevskiy Ave., 153012, Ivanovo, Russian Federation
| | - D B Berezin
- Institute of Macroheterocyclic Compounds, Ivanovo State University of Chemistry and Technology (ISUCT), 7, Sheremetevskiy Ave., 153012, Ivanovo, Russian Federation
| |
Collapse
|
|
7
|
Savelyeva IO, Zhdanova KA, Gradova MA, Gradov OV, Bragina NA. Cationic Porphyrins as Antimicrobial and Antiviral Agents in Photodynamic Therapy. Curr Issues Mol Biol 2023; 45:9793-9822. [PMID: 38132458 PMCID: PMC10741785 DOI: 10.3390/cimb45120612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/30/2023] [Accepted: 12/01/2023] [Indexed: 12/23/2023] Open
Abstract
Antimicrobial photodynamic therapy (APDT) has received a great deal of attention due to its unique ability to kill all currently known classes of microorganisms. To date, infectious diseases caused by bacteria and viruses are one of the main sources of high mortality, mass epidemics and global pandemics among humans. Every year, the emergence of three to four previously unknown species of viruses dangerous to humans is recorded, totaling more than 2/3 of all newly discovered human pathogens. The emergence of bacteria with multidrug resistance leads to the rapid obsolescence of antibiotics and the need to create new types of antibiotics. From this point of view, photodynamic inactivation of viruses and bacteria is of particular interest. This review summarizes the most relevant mechanisms of antiviral and antibacterial action of APDT, molecular targets and correlation between the structure of cationic porphyrins and their photodynamic activity.
Collapse
Affiliation(s)
- Inga O. Savelyeva
- Institute of Fine Chemical Technology, MIREA—Russian Technological University, Vernadsky Prospect 86, Moscow 119571, Russia; (I.O.S.); (K.A.Z.); (N.A.B.)
| | - Kseniya A. Zhdanova
- Institute of Fine Chemical Technology, MIREA—Russian Technological University, Vernadsky Prospect 86, Moscow 119571, Russia; (I.O.S.); (K.A.Z.); (N.A.B.)
| | - Margarita A. Gradova
- N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Kosygin Street 4, Moscow 119991, Russia;
| | - Oleg V. Gradov
- N.N. Semenov Federal Research Center for Chemical Physics, Russian Academy of Sciences, Kosygin Street 4, Moscow 119991, Russia;
| | - Natal’ya A. Bragina
- Institute of Fine Chemical Technology, MIREA—Russian Technological University, Vernadsky Prospect 86, Moscow 119571, Russia; (I.O.S.); (K.A.Z.); (N.A.B.)
| |
Collapse
|
|
8
|
Aung W, Tsuji AB, Rikiyama K, Nishikido F, Obara S, Higashi T. Imaging assessment of photosensitizer emission induced by radionuclide-derived Cherenkov radiation using charge-coupled device optical imaging and long-pass filters. World J Radiol 2023; 15:315-323. [PMID: 38058603 PMCID: PMC10696188 DOI: 10.4329/wjr.v15.i11.315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 10/26/2023] [Accepted: 11/17/2023] [Indexed: 11/24/2023] Open
Abstract
BACKGROUND Radionuclides produce Cherenkov radiation (CR), which can potentially activate photosensitizers (PSs) in phototherapy. Several groups have studied Cherenkov energy transfer to PSs using optical imaging; however, cost-effectively identifying whether PSs are excited by radionuclide-derived CR and detecting fluorescence emission from excited PSs remain a challenge. Many laboratories face the need for expensive dedicated equipment. AIM To cost-effectively confirm whether PSs are excited by radionuclide-derived CR and distinguish fluorescence emission from excited PSs. METHODS The absorbance and fluorescence spectra of PSs were measured using a microplate reader and fluorescence spectrometer to examine the photo-physical properties of PSs. To mitigate the need for expensive dedicated equipment and achieve the aim of the study, we developed a method that utilizes a charge-coupled device optical imaging system and appropriate long-pass filters of different wavelengths (manual sequential application of long-pass filters of 515, 580, 645, 700, 750, and 800 nm). Tetrakis (4-carboxyphenyl) porphyrin (TCPP) was utilized as a model PS. Different doses of copper-64 (64CuCl2) (4, 2, and 1 mCi) were used as CR-producing radionuclides. Imaging and data acquisition were performed 0.5 h after sample preparation. Differential image analysis was conducted by using ImageJ software (National Institutes of Health) to visually evaluate TCPP fluorescence. RESULTS The maximum absorbance of TCPP was at 390-430 nm, and the emission peak was at 670 nm. The CR and CR-induced TCPP emissions were observed using the optical imaging system and the high-transmittance long-pass filters described above. The emission spectra of TCPP with a peak in the 645-700 nm window were obtained by calculation and subtraction based on the serial signal intensity (total flux) difference between 64CuCl2 + TCPP and 64CuCl2. Moreover, the differential fluorescence images of TCPP were obtained by subtracting the 64CuCl2 image from the 64CuCl2 + TCPP image. The experimental results considering different 64CuCl2 doses showed a dose-dependent trend. These results demonstrate that a bioluminescence imaging device coupled with different long-pass filters and subtraction image processing can confirm the emission spectra and differential fluorescence images of CR-induced TCPP. CONCLUSION This simple method identifies the PS fluorescence emission generated by radionuclide-derived CR and can contribute to accelerating the development of Cherenkov energy transfer imaging and the discovery of new PSs.
Collapse
Affiliation(s)
- Winn Aung
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
| | - Atsushi B Tsuji
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
| | - Kazuaki Rikiyama
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
| | - Fumihiko Nishikido
- Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
| | - Satoshi Obara
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
| | - Tatsuya Higashi
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan
| |
Collapse
|
|
9
|
Moura NMM, Moreira X, Da Silva ES, Faria JL, Neves MGPMS, Almeida A, Faustino MAF, Gomes ATPC. Efficient Strategies to Use β-Cationic Porphyrin-Imidazolium Derivatives in the Photoinactivation of Methicillin-Resistant Staphylococcus aureus. Int J Mol Sci 2023; 24:15970. [PMID: 37958951 PMCID: PMC10647407 DOI: 10.3390/ijms242115970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 10/27/2023] [Accepted: 11/02/2023] [Indexed: 11/15/2023] Open
Abstract
Bacterial resistance to antibiotics is a critical global health issue and the development of alternatives to conventional antibiotics is of the upmost relevance. Antimicrobial photodynamic therapy (aPDT) is considered a promising and innovative approach for the photoinactivation of microorganisms, particularly in cases where traditional antibiotics may be less effective due to resistance or other limitations. In this study, two β-modified monocharged porphyrin-imidazolium derivatives were efficiently incorporated into polyvinylpyrrolidone (PVP) formulations and supported into graphitic carbon nitride materials. Both porphyrin-imidazolium derivatives displayed remarkable photostability and the ability to generate cytotoxic singlet oxygen. These properties, which have an important impact on achieving an efficient photodynamic effect, were not compromised after incorporation/immobilization. The prepared PVP-porphyrin formulations and the graphitic carbon nitride-based materials displayed excellent performance as photosensitizers to photoinactivate methicillin-resistant Staphylococcus aureus (MRSA) (99.9999% of bacteria) throughout the antimicrobial photodynamic therapy. In each matrix, the most rapid action against S. aureus was observed when using PS 2. The PVP-2 formulation needed 10 min of exposure to white light at 5.0 µm, while the graphitic carbon nitride hybrid GCNM-2 required 20 min at 25.0 µm to achieve a similar level of response. These findings suggest the potential of graphitic carbon nitride-porphyrinic hybrids to be used in the environmental or clinical fields, avoiding the use of organic solvents, and might allow for their recovery after treatment, improving their applicability for bacteria photoinactivation.
Collapse
Affiliation(s)
- Nuno M. M. Moura
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal; (X.M.); (M.G.P.M.S.N.); (M.A.F.F.)
| | - Xavier Moreira
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal; (X.M.); (M.G.P.M.S.N.); (M.A.F.F.)
- Department of Biology and CESAM, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal;
| | - Eliana Sousa Da Silva
- LSRE-LCM—Laboratory of Separation and Reaction Engineering-Laboratory of Catalysis and Materials, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal; (E.S.D.S.); (J.L.F.)
- ALiCE—Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
| | - Joaquim Luís Faria
- LSRE-LCM—Laboratory of Separation and Reaction Engineering-Laboratory of Catalysis and Materials, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto, Portugal; (E.S.D.S.); (J.L.F.)
- ALiCE—Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
| | - Maria G. P. M. S. Neves
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal; (X.M.); (M.G.P.M.S.N.); (M.A.F.F.)
| | - Adelaide Almeida
- Department of Biology and CESAM, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal;
| | - Maria A. F. Faustino
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal; (X.M.); (M.G.P.M.S.N.); (M.A.F.F.)
| | - Ana T. P. C. Gomes
- Department of Biology and CESAM, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal;
| |
Collapse
|
|
10
|
Kumar A, Mondal A, Douglass ME, Francis DJ, Garren MR, Estes Bright LM, Ghalei S, Xie J, Brisbois EJ, Handa H. Nanoarchitectonics of nitric oxide releasing supramolecular structures for enhanced antibacterial efficacy under visible light irradiation. J Colloid Interface Sci 2023; 640:144-161. [PMID: 36842420 PMCID: PMC10081829 DOI: 10.1016/j.jcis.2023.02.083] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/13/2023] [Accepted: 02/15/2023] [Indexed: 02/22/2023]
Abstract
Light-controlled therapies offer a promising strategy to prevent and suppress infections caused by numerous bacterial pathogens. Excitation of exogenously supplied photosensitizers (PS) at specific wavelengths elicits levels of reactive oxygen intermediates toxic to bacteria. Porphyrin-based supramolecular nanostructure frameworks (SNF) are effective PS with unique physicochemical properties that have led to their widespread use in photomedicine. Herein, we developed a nitric oxide (NO) releasing, biocompatible, and stable porphyrin-based SNF (SNF-NO), which was achieved through a confined noncovalent self-assembly process based on π-π stacking. Characterization of the SNFs via scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis showed the formation of three-dimensional, well-defined octahedral structures. These SNF-NO were shown to exhibit a red shift due to the noncovalent self-assembly of porphyrins, which also show extended light absorption to broadly cover the entire visible light spectrum to enhance photodynamic therapy (PDT). Under visible light irradiation (46 J cm-2), the SNF generates high yields of singlet oxygen (1O2) radicals, hydroxyl radicals (HO), superoxide radicals (O2), and peroxynitrite (ONOO-) radicals that have shown potential to enhance antimicrobial photodynamic therapy (APDT) against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli (E. coli). The resulting SNFs also exhibit significant biofilm dispersion and a decrease in biomass production. The combination of robust photosensitizer SNFs with nitric oxide-releasing capabilities is dynamic in its ability to target pathogenic infections while remaining nontoxic to mammalian cells. The engineered SNFs have enormous potential for treating and managing microbial infections.
Collapse
Affiliation(s)
- Anil Kumar
- School of Chemical Materials and Biomedical Engineering, University of Georgia, Athens, GA 30602, United States
| | - Arnab Mondal
- School of Chemical Materials and Biomedical Engineering, University of Georgia, Athens, GA 30602, United States
| | - Megan E Douglass
- School of Chemical Materials and Biomedical Engineering, University of Georgia, Athens, GA 30602, United States
| | - Divine J Francis
- Department of Chemistry, University of Georgia, Athens, GA 30602, United States
| | - Mark R Garren
- School of Chemical Materials and Biomedical Engineering, University of Georgia, Athens, GA 30602, United States
| | - Lori M Estes Bright
- School of Chemical Materials and Biomedical Engineering, University of Georgia, Athens, GA 30602, United States
| | - Sama Ghalei
- School of Chemical Materials and Biomedical Engineering, University of Georgia, Athens, GA 30602, United States
| | - Jin Xie
- Department of Chemistry, University of Georgia, Athens, GA 30602, United States
| | - Elizabeth J Brisbois
- School of Chemical Materials and Biomedical Engineering, University of Georgia, Athens, GA 30602, United States
| | - Hitesh Handa
- School of Chemical Materials and Biomedical Engineering, University of Georgia, Athens, GA 30602, United States.
| |
Collapse
|
|
11
|
Meng S, Xu Z, Wang X, Liu Y, Li B, Zhang J, Zhang X, Liu T. Synthesis and photodynamic antimicrobial chemotherapy against multi-drug resistant Proteus mirabilis of ornithine-porphyrin conjugates in vitro and in vivo. Front Microbiol 2023; 14:1196072. [PMID: 37362917 PMCID: PMC10285166 DOI: 10.3389/fmicb.2023.1196072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 05/18/2023] [Indexed: 06/28/2023] Open
Abstract
For the treatment of bacterial infections, photodynamic antimicrobial chemotherapy (PACT) has the advantage of circumventing multi-drug resistance. In this work, new cationic photosensitizers against multi-drug resistant Proteus mirabilis (MRPM) were designed and synthesized by the conjugation of amino phenyl porphyrin with basic amino acid L-ornithine. Their photoinactivation efficacies against MRPM in vitro were reported and include the influence of laser energy, uptake, MIC and MBC, dose-dependent photoinactivation effects, membrane integrity, and fluorescence imaging. The PACT in vivo was evaluated using a wound mouse model infected by MRPM. Photosensitizer 4d displayed high photo inactivation efficacy against MRPM at 7.81 μM under illumination, and it could accelerate wound healing via bactericidal effect. These ornithine-porphyrin conjugates are potential photosensitizers for PACT in the treatment of MRPM infection.
Collapse
Affiliation(s)
- Shuai Meng
- Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
- Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Zengping Xu
- Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
- Center for Drug Evaluation, National Medical Products Administration, Beijing, China
| | - Xueming Wang
- Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Yang Liu
- Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| | - Bole Li
- Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Jie Zhang
- Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Xiaolong Zhang
- Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Tianjun Liu
- Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
| |
Collapse
|
|
12
|
Yang F, Xu M, Chen X, Luo Y. Spotlight on porphyrins: Classifications, mechanisms and medical applications. Biomed Pharmacother 2023; 164:114933. [PMID: 37236030 DOI: 10.1016/j.biopha.2023.114933] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 05/11/2023] [Accepted: 05/22/2023] [Indexed: 05/28/2023] Open
Abstract
Photodynamic therapy (PDT) and sonodynamic therapy (SDT) are non-invasive treatment methods with obvious inhibitory effect on tumors and have few side effects, which have been widely concerned and explored by researchers. Sensitizer is the main factor in determining the therapeutic effect of PDT and SDT. Porphyrins, a group of organic compounds widespread in nature, can be activated by light or ultrasound and produce reactive oxygen species. Therefore, porphyrins as sensitizers in PDT have been widely explored and investigated for many years. Herein, we summarize the classical porphyrin compounds and their applications and mechanisms in PDT and SDT. The application of porphyrin in clinical diagnosis and imaging is also discussed. In conclusion, porphyrins have good application prospects in disease treatment as an important part of PDT or SDT, and in clinical diagnosis and imaging.
Collapse
Affiliation(s)
- Fuyu Yang
- National Health Commission Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin 150001, China
| | - Meiqi Xu
- National Health Commission Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin 150001, China
| | - Xiaoyu Chen
- Department of Neonatal, The Fourth Hospital of Harbin Medical University, Harbin
| | - Yakun Luo
- National Health Commission Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin 150001, China.
| |
Collapse
|
|
13
|
Gu X, Xu L, Yuan H, Li C, Zhao J, Li S, Yu D. Sophorolipid-toluidine blue conjugates for improved antibacterial photodynamic therapy through high accumulation. RSC Adv 2023; 13:11782-11793. [PMID: 37077994 PMCID: PMC10106977 DOI: 10.1039/d3ra01618h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Accepted: 04/10/2023] [Indexed: 04/21/2023] Open
Abstract
Anti-bacterial photodynamic therapy is the most promising treatment protocol for bacterial infection, but low accumulation of photosensitizers has seriously hindered their development in clinical application. Here, with inherent outstanding affinity to bacterial cell envelope, sophorolipid produced from Candida bombicola has been conjugated to toluidine blue (SL-TB) through amidation reaction. The structure of SL-TB conjugates was identified by 1H-NMR, FT-IR and ESI-HRMS. The interfacial assembly and photophysical properties of SL-TB conjugates have been disclosed through surface tension, micro-polarity, electronic and fluorescence spectra. After light irradiation, the log10 (reduced CFU) of free toluidine blue to P. aeruginosa and S. aureus were 4.5 and 7.9, respectively. In contrast, SL-TB conjugates showed a higher bactericidal activity, with a reduction of 6.3 and 9.7 log10 units of CFU against P. aeruginosa and S. aureus, respectively. The fluorescence quantitative results showed that SL-TB could accumulate 2850 nmol/1011 cells and 4360 nmol/1011 cells by P. aeruginosa and S. aureus, which was much higher than the accumulation of 462 nmol/1011 cells and 827 nmol/1011 cells of free toluidine blue. Through the cooperation of triple factors, including sophorose affinity to bacterial cells, hydrophobic association with plasma membrane, and electrostatic attraction, higher SL-TB accumulation was acquired, which has enhanced antibacterial photodynamic efficiencies.
Collapse
Affiliation(s)
- Xiaoxiao Gu
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University Nanjing 211816 PR China +86-25-58139386
| | - Lixian Xu
- Department of Dermatology, The Second Affiliated Hospital of Nanjing Medical University No.121 Jiangjiayuan Road Nanjing 210000 P. R. China
| | - Haoyang Yuan
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University Nanjing 211816 PR China +86-25-58139386
| | - Cailing Li
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University Nanjing 211816 PR China +86-25-58139386
| | - Juan Zhao
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University Nanjing 211816 PR China +86-25-58139386
| | - Shuang Li
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University Nanjing 211816 PR China +86-25-58139386
| | - Dinghua Yu
- College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University Nanjing 211816 PR China +86-25-58139386
| |
Collapse
|
|
14
|
Frant MP, Trytek M, Deryło K, Kutyła M, Paduch R. Cellular Localization of Selected Porphyrins and Their Effect on the In Vitro Motility of Human Colon Tumors and Normal Cells. Molecules 2023; 28:molecules28072907. [PMID: 37049670 PMCID: PMC10096141 DOI: 10.3390/molecules28072907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 03/13/2023] [Accepted: 03/22/2023] [Indexed: 04/14/2023] Open
Abstract
Standard therapies for colorectal cancer cannot eliminate or sufficiently reduce the metastasis process. Photodynamic therapy (PDT) may be an alternative to minimizing this problem. Here, we examined the cellular localization of selected porphyrins and determined whether free-base and manganese (III) metallated porphyrins may limit colon cancer cells' (HT29) or normal colon epithelial cells' (CCD 841 CoTr) motility in vitro. White light irradiation was used to initiate the photodynamic effect. Porphyrin uptake by the cells was determined by porphyrin fluorescence measurements through the use of confocal microscopy. Free-base porphyrin was found in cells, where it initially localized at the edge of the cytoplasm and later in the perinuclear area. The concentrations of porphyrins had no effect on cancer cell migration but had a significant effect on normal cell motility. Due to the low concentrations of porphyrins used, no changes in F-actin filaments of the cellular cytoskeleton were detected. Signal transmission via connexons between neighbouring cells was limited to a maximum of 40 µm for HT29 and 30 µm for CCD 841 CoTr cells. The tested porphyrins differed in their activity against the tumor and normal cells' migration capacity. Depending on the porphyrin used and the type of cells, their migration changed in relation to the control sample. The use of white light may change the activity of the porphyrins relative to the migratory capacity of the cells. The aim of the present study was to analyse the intracellular localization of tested porphyrins and their influence on the mobility of cells after irradiation with harmless white light.
Collapse
Affiliation(s)
- Maciej P Frant
- Department of Swine Diseases, National Veterinary Research Institute, Al. Partyzantów 57, 24-100 Puławy, Poland
| | - Mariusz Trytek
- Department of Industrial and Environmental Microbiology, Institute of Biological Sciences, Maria Curie-Skłodowska University, 20-033 Lublin, Poland
| | - Kamil Deryło
- Department of Molecular Biology, Institute of Biological Sciences, Maria Curie-Skłodowska University, 20-033 Lublin, Poland
| | - Mateusz Kutyła
- Department of Industrial and Environmental Microbiology, Institute of Biological Sciences, Maria Curie-Skłodowska University, 20-033 Lublin, Poland
| | - Roman Paduch
- Department of Virology and Immunology, Institute of Biological Sciences, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland
- Department of General and Pediatric Ophthalmology, Medical University of Lublin, Chmielna 1, 20-079 Lublin, Poland
| |
Collapse
|
|
15
|
MTHPP monoacetic ester: unexpected formation, zinc metalation, thermal and photophysical properties. JOURNAL OF THE IRANIAN CHEMICAL SOCIETY 2023. [DOI: 10.1007/s13738-023-02779-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
AbstractIn the current investigation we report an unexpected methyl esterification occurred during the coupling reaction of mTHPP monoacetic acid 2 with 3-amino-1,2,4-triazole in the presence of HBTU/DIPEA. The mechanism of this unexpected methyl esterification was studied, and the structure of the formed methyl ester 5 was confirmed by the means of 1H, 13C NMR in addition to (MALDI-TOF and ESI-HRMS) spectrometry. The formation of 5 during the coupling reaction was also chemically supported by an alternative synthetic method involving a direct monosubstitution reaction of mTHPP 1 with methyl bromoacetate. We also investigated the metalation of 5 with zinc and studied the thermal properties along with differential scanning calorimetry (DSC) of the zinc porphyrin 6. The photophysical properties of porphyrin methyl ester 5 and its zinc complex 6 were also investigated.
Graphical Abstract
Collapse
|
|
16
|
Jurak I, Cokarić Brdovčak M, Djaković L, Bertović I, Knežević K, Lončarić M, Jurak Begonja A, Malatesti N. Photodynamic Inhibition of Herpes Simplex Virus 1 Infection by Tricationic Amphiphilic Porphyrin with a Long Alkyl Chain. Pharmaceutics 2023; 15:pharmaceutics15030956. [PMID: 36986817 PMCID: PMC10058617 DOI: 10.3390/pharmaceutics15030956] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 03/09/2023] [Accepted: 03/13/2023] [Indexed: 03/18/2023] Open
Abstract
Photodynamic therapy (PDT) is broadly used to treat different tumors, and it is a rapidly developing approach to inactivating or inhibiting the replication of fungi, bacteria, and viruses. Herpes simplex virus 1 (HSV-1) is an important human pathogen and a frequently used model to study the effects of PDT on enveloped viruses. Although many photosensitizers (PSs) have been tested for their antiviral properties, analyses are usually limited to assessing the reduction in viral yield, and thus the molecular mechanisms of photodynamic inactivation (PDI) remain poorly understood. In this study, we investigated the antiviral properties of TMPyP3-C17H35, a tricationic amphiphilic porphyrin-based PS with a long alkyl chain. We show that light-activated TMPyP3-C17H35 can efficiently block virus replication at certain nM concentrations without exerting obvious cytotoxicity. Moreover, we show that the levels of viral proteins (immediate-early, early, and late genes) were greatly reduced in cells treated with subtoxic concentrations of TMPyP3-C17H35, resulting in markedly decreased viral replication. Interestingly, we observed a strong inhibitory effect of TMPyP3-C17H35 on the virus yield only when cells were treated before or shortly after infection. In addition to the antiviral activity of the internalized compound, we show that the compound dramatically reduces the infectivity of free virus in the supernatant. Overall, our results demonstrate that activated TMPyP3-C17H35 effectively inhibits HSV-1 replication and that it can be further developed as a potential novel treatment and used as a model to study photodynamic antimicrobial chemotherapy.
Collapse
Affiliation(s)
- Igor Jurak
- Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, HR-51000 Rijeka, Croatia
- Correspondence:
| | - Maja Cokarić Brdovčak
- Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, HR-51000 Rijeka, Croatia
| | - Lara Djaković
- Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, HR-51000 Rijeka, Croatia
| | - Ivana Bertović
- Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, HR-51000 Rijeka, Croatia
| | - Klaudia Knežević
- Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, HR-51000 Rijeka, Croatia
| | - Martin Lončarić
- Photonics and Quantum Optics Unit, Center of Excellence for Advanced Materials and Sensing Devices, Ruđer Bošković Institute, Bijenička Cesta 54, HR-10000 Zagreb, Croatia
| | - Antonija Jurak Begonja
- Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, HR-51000 Rijeka, Croatia
| | - Nela Malatesti
- Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, HR-51000 Rijeka, Croatia
| |
Collapse
|
|
17
|
Sarı C, Değirmencioğlu İ, Eyüpoğlu FC. Synthesis and characterization of novel Schiff base-silicon (IV) phthalocyanine complex for photodynamic therapy of breast cancer cell lines. Photodiagnosis Photodyn Ther 2023; 42:103504. [PMID: 36907257 DOI: 10.1016/j.pdpdt.2023.103504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 02/16/2023] [Accepted: 03/07/2023] [Indexed: 03/12/2023]
Abstract
BACKGROUND Photodynamic therapy is an alternative anticancer treatment approach that promises high therapeutic efficacy. In this study, it is aimed to investigate the PDT-mediated anticancer effects of newly synthesized silicon phthalocyanine (SiPc) molecules on MDA-MB-231, MCF-7 breast cancer cell lines, and non-tumorigenic MCF-10A breast cell line. METHODS Novel bromo substituted Schiff base (3a), its nitro homolog (3b), and their silicon complexes (SiPc-5a and SiPc-5b) were synthesized. Their proposed structures were confirmed by FT-IR, NMR, UV-vis and MS instrumental techniques. MDA-MB-231, MCF-7 and MCF-10A cells were illuminated at a light wavelength of 680 nm for 10 min, giving a total irradiation dose of 10 j/cm2. MTT assay was used to determine the cytotoxic effects of SiPc-5a and SiPc-5b. Apoptotic cell death was analyzed using flow cytometry. Changes in the mitochondrial membrane potential were determined by TMRE staining. Intracellular ROS generation was observed microscopically using H2DCFDA dye. Colony formation assay and in vitro scratch assay were performed to analyze the clonogenic activity and cell motility. Transwell migration and matrigel invasion analyzes were conducted to observe changes in the migration and invasion status of the cells. RESULTS The combination of SiPc-5a and SiPc-5b with PDT exhibited cytotoxic effects on cancer cells and triggered cell death. SiPc-5a/PDT and SiPc-5b/PDT decreased mitochondrial membrane potential and increased intracellular ROS production. Statistically significant changes were detected in cancer cells' colony-forming ability and motility. SiPc-5a/PDT and SiPc-5b/PDT reduced cancer cells' migration and invasion capacities. CONCLUSION The present study identifies PDT-mediated antiproliferative, apoptotic, and anti-migratory characteristics of novel SiPc molecules. The outcomes of this study emphasize the anticancer properties of these molecules and suggest that they may be evaluated as drug-candidate molecules for therapeutic purposes.
Collapse
Affiliation(s)
- Ceren Sarı
- Department of Medical Biology, Institute of Health Sciences, Karadeniz Technical University, Trabzon, Turkey
| | - İsmail Değirmencioğlu
- Department of Chemistry, Faculty of Sciences, Karadeniz Technical University, Trabzon, Turkey
| | - Figen Celep Eyüpoğlu
- Department of Medical Biology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.
| |
Collapse
|
|
18
|
Yegorov YE, Vishnyakova KS, Pan X, Egorov AE, Popov KV, Tevonyan LL, Chashchina GV, Kaluzhny DN. Mechanisms of Phototoxic Effects of Cationic Porphyrins on Human Cells In Vitro. Molecules 2023; 28:molecules28031090. [PMID: 36770766 PMCID: PMC9921399 DOI: 10.3390/molecules28031090] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 01/17/2023] [Accepted: 01/17/2023] [Indexed: 01/24/2023] Open
Abstract
The toxic effects of four cationic porphyrins on various human cells were studied in vitro. It was found that, under dark conditions, porphyrins are almost nontoxic, while, under the action of light, the toxic effect was observed starting from nanomolar concentrations. At a concentration of 100 nM, porphyrins caused inhibition of metabolism in the MTT test in normal and cancer cells. Furthermore, low concentrations of porphyrins inhibited colony formation. The toxic effect was nonlinear; with increasing concentrations of various porphyrins, up to about 1 μM, the effect reached a plateau. In addition to the MTT test, this was repeated in experiments examining cell permeability to trypan blue, as well as survival after 24 h. The first visible manifestation of the toxic action of porphyrins is blebbing and swelling of cells. Against the background of this process, permeability to porphyrins and trypan blue appears. Subsequently, most cells (even mitotic cells) freeze in this swollen state for a long time (24 and even 48 h), remaining attached. Cellular morphology is mostly preserved. Thus, it is clear that the cells undergo mainly necrotic death. The hypothesis proposed is that the concentration dependence of membrane damage indicates a limited number of porphyrin targets on the membrane. These targets may be any ion channels, which should be considered in photodynamic therapy.
Collapse
Affiliation(s)
- Yegor E. Yegorov
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
- Correspondence: (Y.E.Y.); (D.N.K.)
| | - Khava S. Vishnyakova
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
| | - Xiaowen Pan
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
- Moscow Institute of Physics and Technology, Russian Academy of Sciences, 141701 Dolgoprudny, Russia
| | - Anton E. Egorov
- Emanuel Institute of Biochemical Physics, Russian Academy of Science, 4 Kosygin Street, 119334 Moscow, Russia
| | - Konstantin V. Popov
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I.Kulakov, 4 Oparina Street, 117997 Moscow, Russia
| | - Liana L. Tevonyan
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
- Moscow Institute of Physics and Technology, Russian Academy of Sciences, 141701 Dolgoprudny, Russia
| | - Galina V. Chashchina
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
| | - Dmitry N. Kaluzhny
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
- Correspondence: (Y.E.Y.); (D.N.K.)
| |
Collapse
|
|
19
|
Advances in Liposome-Encapsulated Phthalocyanines for Photodynamic Therapy. Life (Basel) 2023; 13:life13020305. [PMID: 36836662 PMCID: PMC9965606 DOI: 10.3390/life13020305] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 01/12/2023] [Accepted: 01/18/2023] [Indexed: 01/24/2023] Open
Abstract
This updated review aims to describe the current status in the development of liposome-based systems for the targeted delivery of phthalocyanines for photodynamic therapy (PDT). Although a number of other drug delivery systems (DDS) can be found in the literature and have been studied for phthalocyanines or similar photosensitizers (PSs), liposomes are by far the closest to clinical practice. PDT itself finds application not only in the selective destruction of tumour tissues or the treatment of microbial infections, but above all in aesthetic medicine. From the point of view of administration, some PSs can advantageously be delivered through the skin, but for phthalocyanines, systemic administration is more suitable. However, systemic administration places higher demands on advanced DDS, active tissue targeting and reduction of side effects. This review focuses on the already described liposomal DDS for phthalocyanines, but also describes examples of DDS used for structurally related PSs, which can be assumed to be applicable to phthalocyanines as well.
Collapse
|
|
20
|
Zhdanova KA, Savel’eva IO, Usanev AY, Usachev MN, Shmigol TA, Gradova MA, Bragina NA. Synthesis of trans-Substituted Cationic Zinc Porphynates and Study of their Photodynamic Antimicrobial Activity. RUSS J INORG CHEM+ 2022. [DOI: 10.1134/s0036023622601209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
|
|
21
|
Rong J, Wu Y, Ji X, Zhao T, Yin B, Rao Y, Zhou M, Osuka A, Xu L, Song J. Porphyrinatonickel(II)-Cyclopentene and Porphyrinatonickel(II)-Cyclopentadiene Hybrids: Zirconacyclopentadiene-Mediated Syntheses, Structures, and Mechanistic Study. Org Lett 2022; 24:6128-6132. [PMID: 35960173 DOI: 10.1021/acs.orglett.2c02120] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The reaction of meso-formyl Ni(II) porphyrin 1 with zirconacyclopentadiene 2 in the presence of AlCl3 afforded four products 3, 4, 5, and 6 with a total yield of over 85%. The structures of these compounds are well-characterized by 1H NMR an d13C NMR spectroscopy, HRMS, and X-ray single-crystal diffraction. The mechanism is proposed mainly on the basis of isotopic labeling experiments, which showed that a Friedel-Crafts-type reaction and β-H shift may be critical during the formation of 5 and 6.
Collapse
Affiliation(s)
- Jian Rong
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China
| | - Yidan Wu
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China
| | - Xiaoheng Ji
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China
| | - Tingting Zhao
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China
| | - Bangshao Yin
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China
| | - Yutao Rao
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China
| | - Mingbo Zhou
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China
| | - Atsuhiro Osuka
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China
| | - Ling Xu
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China
| | - Jianxin Song
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan 410081, China
| |
Collapse
|
|
22
|
Investigation of Sonosensitizers Based on Phenothiazinium Photosensitizers. APPLIED SCIENCES-BASEL 2022. [DOI: 10.3390/app12157819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
The main advantage of sonodynamic therapy (SDT), the combining of ultrasound with a sonosensitizer, over photodynamic therapy (PDT) is that ultrasound penetrates deeper into tissues to activate the sonosensitizer, which offers noninvasive therapy for tumors in a site-oriented approach. In this study, we synthesized two symmetrical phenothiazine derivatives in which the methyl groups of MB (methylene blue) have been replaced by a hexyl and hydroxyethyl chains, named 3,7-bis(dihexylamino)-phenothiazin-5-ium iodide (MB6C) and 3,7-bis(di(2-hydroxyethyl)amino)-phenothiazin-5-ium iodide (MBOH), respectively. We explore the efficiency differences between PDT and SDT induced by these phenothiazine derivatives based on the standard of methylene blue (MB). Spectral studies indicate that these MB analogs exhibit sonosensitization ability with a similar tendency to the photosensitization ability. This means that MB, MBOH, and MB6C can be potential photosensitizers and sonosensitizers. After biological evaluation, we conclude that compound MB6C is a potential PDT and SDT candidate because it exhibits higher uptake, efficient intracellular phototoxicity and sonotoxicity over MB and MBOH, with IC50 values of ~2.5 µM and ~5 µM, respectively.
Collapse
|
|
23
|
Liu Z, Li H, Tian Z, Liu X, Guo Y, He J, Wang Z, Zhou T, Liu Y. Porphyrin-Based Nanoparticles: A Promising Phototherapy Platform. Chempluschem 2022; 87:e202200156. [PMID: 35997087 DOI: 10.1002/cplu.202200156] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 07/28/2022] [Indexed: 11/10/2022]
Abstract
Phototherapy, including photodynamic therapy and photothermal therapy, is an emerging form of non-invasive treatment. The combination of imaging technology and phototherapy is becoming an attractive development in the treatment of cancer, as it allows for highly effective therapeutic results through image-guided phototherapy. Porphyrins have attracted significant interest in the treatment and diagnosis of cancer due to their excellent phototherapeutic effects in phototherapy and their remarkable imaging capabilities in fluorescence imaging, magnetic resonance imaging and photoacoustic imaging. However, porphyrins suffer from poor water solubility, low near-infrared absorption and insufficient tumor accumulation. The development of nanotechnology provides an effective way to improve the bioavailability, phototherapeutic effect and imaging capability of porphyrins. This review highlights the research results of porphyrin-based small molecule nanoparticles in phototherapy and image-guided phototherapy in the last decade and discusses the challenges and directions for the development of porphyrin-based small molecule nanoparticles in phototherapy.
Collapse
Affiliation(s)
- Zhenhua Liu
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Hui Li
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Zejie Tian
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Xin Liu
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Yu Guo
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Jun He
- Institute of Chemistry & Chemical Engineering, University of South China, Hengyang City, Hunan Province, 421001, P.R. China
| | - Zhenyu Wang
- Institute of Chemistry & Chemical Engineering, University of South China, Hengyang City, Hunan Province, 421001, P.R. China
| | - Tao Zhou
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| | - Yunmei Liu
- Institute of Pharmacy & Pharmacology Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, University of South China, Hengyang City, Hunan Province, 421001, P. R. China
| |
Collapse
|
|
24
|
Ribeiro M, Gomes IB, Saavedra MJ, Simões M. Photodynamic therapy and combinatory treatments for the control of biofilm-associated infections. Lett Appl Microbiol 2022; 75:548-564. [PMID: 35689422 DOI: 10.1111/lam.13762] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 04/26/2022] [Accepted: 05/26/2022] [Indexed: 12/20/2022]
Abstract
The advent of antimicrobial resistance has added considerable impact to infectious diseases both in the number of infections and healthcare costs. Furthermore, the relentless emergence of multidrug-resistant bacteria, particularly in the biofilm state, has made mandatory the discovery of new alternative antimicrobial therapies that are capable to eradicate resistant bacteria and impair the development of new forms of resistance. Amongst the therapeutic strategies for treating biofilms, antimicrobial photodynamic therapy (aPDT) has shown great potential in inactivating several clinically relevant micro-organisms, including antibiotic-resistant 'priority bacteria' declared by the WHO as critical pathogens. Its antimicrobial effect is centred on the basis that harmless low-intensity light stimulates a non-toxic dye named photosensitizer, triggering the production of reactive oxygen species upon photostimulation. In addition, combination therapies of aPDT with other antimicrobial agents (e.g. antibiotics) have also drawn considerable attention, as it is a multi-target strategy. Therefore, the present review highlights the recent advances of aPDT against biofilms, also covering progress on combination therapy.
Collapse
Affiliation(s)
- M Ribeiro
- LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal.,ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Porto, Portugal.,CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal
| | - I B Gomes
- LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal.,ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Porto, Portugal
| | - M J Saavedra
- Department of Veterinary Sciences, School of Agriculture and Veterinary Science, UTAD, Vila Real, Portugal.,Centre for the Research and Technology for Agro-Environment and Biological Sciences (CITAB), UTAD, Vila Real, Portugal
| | - M Simões
- LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal.,ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Porto, Portugal
| |
Collapse
|
|
25
|
Ratkaj I, Mušković M, Malatesti N. Targeting Microenvironment of Melanoma and Head and Neck Cancers
in Photodynamic Therapy. Curr Med Chem 2022; 29:3261-3299. [DOI: 10.2174/0929867328666210709113032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 05/23/2021] [Accepted: 05/26/2021] [Indexed: 11/22/2022]
Abstract
Background:
Photodynamic therapy (PDT), in comparison to other skin cancers,
is still far less effective for melanoma, due to the strong absorbance and the role of
melanin in cytoprotection. The tumour microenvironment (TME) has a significant role in
tumour progression, and the hypoxic TME is one of the main reasons for melanoma progression
to metastasis and its resistance to PDT. Hypoxia is also a feature of solid tumours
in the head and neck region that indicates negative prognosis.
Objective:
The aim of this study was to individuate and describe systematically the main
strategies in targeting the TME, especially hypoxia, in PDT against melanoma and head
and neck cancers (HNC), and assess the current success in their application.
Methods:
PubMed was used for searching, in MEDLINE and other databases, for the
most recent publications on PDT against melanoma and HNC in combination with the
TME targeting and hypoxia.
Results:
In PDT for melanoma and HNC, it is very important to control hypoxia levels,
and amongst the different approaches, oxygen self-supply systems are often applied. Vascular
targeting is promising, but to improve it, optimal drug-light interval, and formulation
to increase the accumulation of the photosensitiser in the tumour vasculature, have to
be established. On the other side, the use of angiogenesis inhibitors, such as those interfering
with VEGF signalling, is somewhat less successful than expected and needs to be
further investigated.
Conclusion:
The combination of PDT with immunotherapy by using multifunctional nanoparticles
continues to develop and seems to be the most promising for achieving a
complete and lasting antitumour effect.
Collapse
Affiliation(s)
- Ivana Ratkaj
- Department of Biotechnology, University of Rijeka, Rijeka, Croatia
| | - Martina Mušković
- Department of Biotechnology, University of Rijeka, Rijeka, Croatia
| | - Nela Malatesti
- Department of Biotechnology, University of Rijeka, Rijeka, Croatia
| |
Collapse
|
|
26
|
Sengupta D, Rai M, Hoque Mazumdar Z, Sharma D, Malabika Singha K, Pandey P, Gaur R. Two cationic meso-thiophenium porphyrins and their zinc-complexes as anti-HIV-1 and antibacterial agents under non-photodynamic therapy (PDT) conditions. Bioorg Med Chem Lett 2022; 65:128699. [PMID: 35341921 DOI: 10.1016/j.bmcl.2022.128699] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 03/16/2022] [Accepted: 03/23/2022] [Indexed: 11/02/2022]
Abstract
The anti-HIV-1 and antimicrobial activities of novel cationic meso-thiophenium porphyrins and their zinc-complex are reported under in vitro non-photodynamic (PDT) conditions. While all the cationic porphyrins led to the inhibition of de novo virus infection, the Zn(II)-complexes of T2(OH)2M (A2B2-type) and T(OH)3M (AB3-type) displayed potent inhibition of HIV-1 entry with T2(OH)2MZn displaying maximal anti-HIV activity. The Zinc complex of both the thiophenium porphyrins T2(OH)2M and T(OH)3M also depicted antibacterial activities against Escherichia coli (ATCC 25922) and more prominently against Staphylococcus aureus (ATCC 25923). Again, the antibacterial activity was more potent for T2(OH)2MZn. Our study highlighted that the presence of two thiophenium groups at the meso-positions of the A2B2-type porphyrins along with zinc strongly enhanced anti-HIV and antimicrobial properties of these novel thiophenium porphyrins under non-PDT conditions.
Collapse
Affiliation(s)
- Devashish Sengupta
- Department of Chemistry, Assam University, Silchar, Assam 788011, India.
| | - Madhu Rai
- Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi 110021, India
| | | | - Debdulal Sharma
- Department of Chemistry, Assam University, Silchar, Assam 788011, India
| | - K Malabika Singha
- Department of Microbiology, Assam University, Silchar, Assam 788011, India
| | - Piyush Pandey
- Department of Microbiology, Assam University, Silchar, Assam 788011, India.
| | - Ritu Gaur
- Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi 110021, India.
| |
Collapse
|
|
27
|
Wu Y, Zhao T, Rong J, Rao Y, Zhou M, Yin B, Ni X, Osuka A, Xu L, Song J. Low-Valent Zirconocene-Mediated Synthesis of Porphyrin(2.1.2.1)s and Its Extension to Synthesis of a Porphyrin(2.1.2.1) Nanobarrel. Angew Chem Int Ed Engl 2022; 61:e202201327. [PMID: 35245411 DOI: 10.1002/anie.202201327] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Indexed: 11/11/2022]
Abstract
Rosenthal's-reagent-mediated intramolecular cyclometallation of α,α-dialkynyldipyrrin nickel(II) complex and subsequent acid treatment afforded a 1,3-butadiene-embedded porphyrin(2.1.2.1), 6, which served as a reactive diene towards dienophiles such as dimethyl acetylenedicarboxylate (DMAD) and benzyne to give corresponding Diels-Alder adducts. Diels-Alder reaction of 6 and benzdiyne gave adducts 14, 15 a, and 15 b along with a trace amount of porphyrin(2.1.2.1) barrel 13. Stepwise routes using 14 or 15 a/15 b as a substrate allowed for the synthesis of 13 as a single stereoisomer. The nanobarrel structure for 13 was revealed by X-ray diffraction, where its cavity held two chloroform molecules via C-H⋅⋅⋅π interaction. DFT calculations revealed that the electrostatic attraction was dominant with binding energy of 32.8 kcal mol-1 .
Collapse
Affiliation(s)
- Yidan Wu
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China
| | - Tingting Zhao
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China
| | - Jian Rong
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China
| | - Yutao Rao
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China
| | - Mingbo Zhou
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China
| | - Bangshao Yin
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China
| | - Xinlong Ni
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China
| | - Atsuhiro Osuka
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China
| | - Ling Xu
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China
| | - Jianxin Song
- Key Laboratory of Chemical Biology and Traditional Chinese Medicine, Ministry of Educational of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China
| |
Collapse
|
|
28
|
Song J, Wu Y, Zhao T, Zhou M, Rong J, Yin B, Ni X, Osuka A, Xu L, Rao Y. Low‐Valent Zirconocene‐mediated Synthesis of Porphyrin(2.1.2.1)s and Its Extension to Synthesis of a Porphyrin(2.1.2.1) Nanobarrel. Angew Chem Int Ed Engl 2022. [DOI: 10.1002/ange.202201327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Jianxin Song
- Hunan Normal University Chemistry Yue Lu Qu Lushan Road 36 410081 Changsha CHINA
| | - Yidan Wu
- Hunan Normal University - Erliban Campus: Hunan Normal University Chemistry CHINA
| | - Tingting Zhao
- Hunan Normal University - Erliban Campus: Hunan Normal University Chemistry CHINA
| | - Mingbo Zhou
- Hunan Normal University - Erliban Campus: Hunan Normal University Chemistry CHINA
| | - Jian Rong
- Hunan Normal University - Erliban Campus: Hunan Normal University Chemistry CHINA
| | - Bangshao Yin
- Hunan Normal University - Erliban Campus: Hunan Normal University Chemistry CHINA
| | - xinlong Ni
- Hunan Normal University - Erliban Campus: Hunan Normal University Chemistry CHINA
| | - Atsuhiro Osuka
- Hunan Normal University - Erliban Campus: Hunan Normal University Chemistry CHINA
| | - Ling Xu
- Hunan Normal University - Erliban Campus: Hunan Normal University Chemistry CHINA
| | - Yutao Rao
- Hunan Normal University - Erliban Campus: Hunan Normal University Chemistry CHINA
| |
Collapse
|
|
29
|
Delcanale P, Abbruzzetti S, Viappiani C. Photodynamic treatment of pathogens. LA RIVISTA DEL NUOVO CIMENTO 2022; 45:407-459. [PMCID: PMC8921710 DOI: 10.1007/s40766-022-00031-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 01/10/2022] [Indexed: 06/01/2023]
Abstract
The current viral pandemic has highlighted the compelling need for effective and versatile treatments, that can be quickly tuned to tackle new threats, and are robust against mutations. Development of such treatments is made even more urgent in view of the decreasing effectiveness of current antibiotics, that makes microbial infections the next emerging global threat. Photodynamic effect is one such method. It relies on physical processes proceeding from excited states of particular organic molecules, called photosensitizers, generated upon absorption of visible or near infrared light. The excited states of these molecules, tailored to undergo efficient intersystem crossing, interact with molecular oxygen and generate short lived reactive oxygen species (ROS), mostly singlet oxygen. These species are highly cytotoxic through non-specific oxidation reactions and constitute the basis of the treatment. In spite of the apparent simplicity of the principle, the method still has to face important challenges. For instance, the short lifetime of ROS means that the photosensitizer must reach the target within a few tens nanometers, which requires proper molecular engineering at the nanoscale level. Photoactive nanostructures thus engineered should ideally comprise a functionality that turns the system into a theranostic means, for instance, through introduction of fluorophores suitable for nanoscopy. We discuss the principles of the method and the current molecular strategies that have been and still are being explored in antimicrobial and antiviral photodynamic treatment.
Collapse
Affiliation(s)
- Pietro Delcanale
- Dipartimento di Scienze Matematiche, Fisiche e Informatiche, Università degli Studi di Parma, Parco Area delle Scienze 7A, 43124 Parma, Italy
| | - Stefania Abbruzzetti
- Dipartimento di Scienze Matematiche, Fisiche e Informatiche, Università degli Studi di Parma, Parco Area delle Scienze 7A, 43124 Parma, Italy
| | - Cristiano Viappiani
- Dipartimento di Scienze Matematiche, Fisiche e Informatiche, Università degli Studi di Parma, Parco Area delle Scienze 7A, 43124 Parma, Italy
| |
Collapse
|
|
30
|
Babu B, Mack J, Nyokong T. A Sn( iv) porphyrin with mitochondria targeting properties for enhanced photodynamic activity against MCF-7 cells. NEW J CHEM 2022. [DOI: 10.1039/d2nj00350c] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
A Sn(iv) porphyrin with a mitochondria targeting triphenylphosphonium moiety has a high ΦΔ value (ca. 0.72) and does not aggregate in aqueous solution. The dye exhibits favorable photodynamic activity against MCF-7 cells with an IC50 value of 2.9 μM.
Collapse
Affiliation(s)
- Balaji Babu
- Institute for Nanotechnology Innovation, Department of Chemistry, Rhodes University, Makhanda 6140, South Africa
| | - John Mack
- Institute for Nanotechnology Innovation, Department of Chemistry, Rhodes University, Makhanda 6140, South Africa
| | - Tebello Nyokong
- Institute for Nanotechnology Innovation, Department of Chemistry, Rhodes University, Makhanda 6140, South Africa
| |
Collapse
|
|
31
|
Yabaş E, Şahin-Bölükbaşı S, Şahin-İnan ZD. New water soluble magnesium phthalocyanine as a potential anticancer drug: Cytotoxic and apoptotic effect on different cancer cell lines. J PORPHYR PHTHALOCYA 2021. [DOI: 10.1142/s1088424621500863] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Although phthalocyanines are usually used a photosensitizers for photodynamic therapy, these works focus on the directly cytotoxic effect of a new water-soluble magnesium phthalocyanine. The new water-soluble magnesium phthalocyanine 2 was synthesized, characterized and investigated for cytotoxic and apoptotic activities. The cytotoxic activities of the compound 2 were determined by using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay on human breast cancer cells (MDA-MB-231, MCF-7), human prostate cancer cells (PC-3), and human healthy lung fibroblast cells (WI-38). The cells were plated and treated 1 to 20 [Formula: see text]M of different concentrations of the compound. MTT assay results indicated that the compound 2 has concentration and time-dependent cytotoxic activities against cancer cells. We also observed that the compound displayed lower toxicity against WI-38 healthy cells than cancer cells at 48 and 72 h. The compound showed a significant cytotoxic activity difference between breast cancer cells and WI-38 healthy cells at 48 and 72 h. Selectivity index of the compound 2 against MCF-7 for 72 h was calculated ¿ 15.62. We also studied the apoptotic and necrotic effect of compound 2using TUNEL and PI staining, respectively. It was found that the synthesized compound 2 increased apoptotic and necrotic cells.
Collapse
Affiliation(s)
- Ebru Yabaş
- Advanced Technology Application and Research Center, Sivas Cumhuriyet University, 58140 Sivas, Turkey
| | - Serap Şahin-Bölükbaşı
- Department of Biochemistry, Faculty of Pharmacy, Sivas Cumhuriyet University, 58140 Sivas, Turkey
| | - Zeynep Deniz Şahin-İnan
- Department of Histology & Embryology, Medicine Faculty, Sivas Cumhuriyet University, 58140 Sivas, Turkey
| |
Collapse
|
|
32
|
Habib A, Serniabad S, Khan MS, Islam R, Chakraborty M, Nargis A, Quayum ME, Alam MA, rapozzi V, Tabata M. Kinetics and mechanism of formation of nickel(II)porphyrin and its interaction with DNA in aqueous medium. J CHEM SCI 2021; 133:83. [PMID: 34366601 PMCID: PMC8329907 DOI: 10.1007/s12039-021-01945-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 05/24/2021] [Accepted: 05/25/2021] [Indexed: 11/25/2022]
Abstract
Kinetics between 5,10,15,20-tetrakis(N-methylpyridium-4-yl)porphyrin and Ni2+ species were investigated in aqueous solution at 25 ±1 °C in I = 0.10 M (NaNO3). Speciation of Ni2+ was done in I = 0.10 M (NaNO3) for knowing distribution of Ni2+ species with solution pH. Experimental data were compared with speciation diagram constructed from the values of hydrolysis constants of Ni2+ ion. Speciation data showed that hexaaquanickel(II) ions took place in hydrolysis reactions through formation of [Ni(OH2)6-n(OH)n]2-n species with solution pH. According to speciation of Ni2+ and pH dependent rate constants, rate expression can be written as: d[Ni(TMPyP)4+]/dt = (k1[Ni2+(aq)] + k2[Ni(OH)+(aq)] + k3[Ni(OH)2o(aq)] + k4[Ni(OH)3-(aq)])[H2TMPyP4+], where k1, k2, k3 and k4 were found to be k1 = (0.62 ± 0.22) × 10-2; k2 = (3.60 ± 0.40) × 10-2; k3 = (2.09 ± 0.52) × 10-2, k4 = (0.53 ± 0.04) × 10-2 M-1s-1 at 25 ±1 °C, respectively. Formation of hydrogen bonding between [Ni(H2O)5(OH)]+ and [H2TMPyP]4+ causes enhanced reactivity. Rate of formation of [Ni(II)TMPyP]4+ complex was to be 3.99 × 10-2 M-1s-1 in I = 0.10 M, NaNO3 (25 ± 1 °C). UV-Vis and fluorescence data suggested that [Ni(II)TMPyP]4+ and [H2(TMPyP)]4+ interact with DNA via outside binding with self-stacking and intercalation, respectively. SYNOPSIS
Collapse
Affiliation(s)
- Ahsan Habib
- Department of Chemistry, Faculty of Science, University of Dhaka, Dhaka, 1000 Bangladesh
| | - Salma Serniabad
- Department of Chemistry, Faculty of Science, University of Dhaka, Dhaka, 1000 Bangladesh
- Department of Applied Chemistry and Chemical Engineering, Noakhali Science and Technology University, Noakhali, 3814 Bangladesh
| | - Mohammad Shamim Khan
- Department of Chemistry, Faculty of Science, University of Dhaka, Dhaka, 1000 Bangladesh
| | - Rokayea Islam
- Department of Chemistry, Faculty of Science, University of Dhaka, Dhaka, 1000 Bangladesh
| | - Mrittika Chakraborty
- Department of Chemistry, Faculty of Science, University of Dhaka, Dhaka, 1000 Bangladesh
| | - Aklima Nargis
- Department of Chemistry, Faculty of Science, University of Dhaka, Dhaka, 1000 Bangladesh
| | - Md Emran Quayum
- Department of Chemistry, Faculty of Science, University of Dhaka, Dhaka, 1000 Bangladesh
| | - Md Ashraful Alam
- Department of Applied Chemistry and Chemical Engineering, Noakhali Science and Technology University, Noakhali, 3814 Bangladesh
| | - Valentina rapozzi
- Department of Medicine, Udine University, P.le Kolbe 4, 33100 Udine, Italy
| | - Masaaki Tabata
- Department of Chemistry, Faculty of Science and Engineering, Saga University, 1, Honjo-machi, Saga, 840-8502 Japan
| |
Collapse
|
|
33
|
Investigation of the triplet excited state and application of cationic meso-tetra(cisplatin)porphyrins in antimicrobial photodynamic therapy. Photodiagnosis Photodyn Ther 2021; 35:102459. [PMID: 34320427 DOI: 10.1016/j.pdpdt.2021.102459] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/08/2021] [Accepted: 07/22/2021] [Indexed: 02/06/2023]
Abstract
In this manuscript, we report, the photophysical study of triplet excited states and antimicrobial photoinactivation of positively charged tetra-cisplatin porphyrin derivatives against Gram + and Gram ‒ bacterial strains. Isomeric cisplatin-porphyrins were used and applied in aPDT assays in the bacilli Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa (Gram negative) and a cocci Staphylococcus aureus (Gram positive) strains. The results show that compound substituted at meta position (3-cis-PtTPyP) is the more efficient photosensitizer against bacteria culture. In this way, tetra-cationic porphyrins containing cisplatin derivatives might be promising aPDT agents with potential applications in clinical infections.
Collapse
|
|
34
|
Magadla A, Babu B, Mack J, Nyokong T. Positively charged styryl pyridine substituted Zn(II) phthalocyanines for photodynamic therapy and photoantimicrobial chemotherapy: effect of the number of charges. Dalton Trans 2021; 50:9129-9136. [PMID: 34115081 DOI: 10.1039/d1dt01047f] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Cationic Zn phthalocyanine complexes were synthesized using Knoevenagel reaction starting from a Zn(ii) tetrakis(2-formylphenoxy)phthalocyanine (1) to form Zn(ii) tetrakis(1-butyl-4-(4-(tetraphenoxy)styryl)pyridin-1-ium) phthalocyanine (2) and Zn(ii) tetrakis(4-(4-(tetraphenoxy)styryl)-1-(4-(triphenylphosphonio)butyl)pyridin-1-ium)phthalocyanine (3). The photophysicochemical behaviours of the Pc complexes were assessed. The cationic complexes display high water-solubility and gave moderate singlet oxygen quantum yield in water. The cationic Pcs demonstrate good cellular uptake and photodynamic activity against MCF-7 cells with IC50 values of 8.2 and 4.9 μM for 2 and 3, respectively. The cationic Pcs also demonstrate high photoantimicrobial activity against Escherichia coli with log reductions of 5.3 and 6.0 for 2 and 3, respectively.
Collapse
Affiliation(s)
- Aviwe Magadla
- Institute for Nanotechnology Innovation. Department of Chemistry, Rhodes University, Makhanda, South Africa.
| | - Balaji Babu
- Institute for Nanotechnology Innovation. Department of Chemistry, Rhodes University, Makhanda, South Africa.
| | - John Mack
- Institute for Nanotechnology Innovation. Department of Chemistry, Rhodes University, Makhanda, South Africa.
| | - Tebello Nyokong
- Institute for Nanotechnology Innovation. Department of Chemistry, Rhodes University, Makhanda, South Africa.
| |
Collapse
|
|
35
|
Mariewskaya KA, Tyurin AP, Chistov AA, Korshun VA, Alferova VA, Ustinov AV. Photosensitizing Antivirals. Molecules 2021; 26:3971. [PMID: 34209713 PMCID: PMC8271894 DOI: 10.3390/molecules26133971] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 06/22/2021] [Accepted: 06/27/2021] [Indexed: 12/23/2022] Open
Abstract
Antiviral action of various photosensitizers is already summarized in several comprehensive reviews, and various mechanisms have been proposed for it. However, a critical consideration of the matter of the area is complicated, since the exact mechanisms are very difficult to explore and clarify, and most publications are of an empirical and "phenomenological" nature, reporting a dependence of the antiviral action on illumination, or a correlation of activity with the photophysical properties of the substances. Of particular interest is substance-assisted photogeneration of highly reactive singlet oxygen (1O2). The damaging action of 1O2 on the lipids of the viral envelope can probably lead to a loss of the ability of the lipid bilayer of enveloped viruses to fuse with the lipid membrane of the host cell. Thus, lipid bilayer-affine 1O2 photosensitizers have prospects as broad-spectrum antivirals against enveloped viruses. In this short review, we want to point out the main types of antiviral photosensitizers with potential affinity to the lipid bilayer and summarize the data on new compounds over the past three years. Further understanding of the data in the field will spur a targeted search for substances with antiviral activity against enveloped viruses among photosensitizers able to bind to the lipid membranes.
Collapse
Affiliation(s)
- Kseniya A. Mariewskaya
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia; (K.A.M.); (A.P.T.); (A.A.C.); (V.A.K.)
- Higher Chemical College of the Russian Academy of Sciences, Mendeleev University of Chemical Technology, Miusskaya sq. 9, 125047 Moscow, Russia
| | - Anton P. Tyurin
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia; (K.A.M.); (A.P.T.); (A.A.C.); (V.A.K.)
- Gause Institute of New Antibiotics, B. Pirogovskaya 11, 119021 Moscow, Russia
| | - Alexey A. Chistov
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia; (K.A.M.); (A.P.T.); (A.A.C.); (V.A.K.)
| | - Vladimir A. Korshun
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia; (K.A.M.); (A.P.T.); (A.A.C.); (V.A.K.)
| | - Vera A. Alferova
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia; (K.A.M.); (A.P.T.); (A.A.C.); (V.A.K.)
- Gause Institute of New Antibiotics, B. Pirogovskaya 11, 119021 Moscow, Russia
| | - Alexey V. Ustinov
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997 Moscow, Russia; (K.A.M.); (A.P.T.); (A.A.C.); (V.A.K.)
| |
Collapse
|
|
36
|
Kirar S, Thakur NS, Reddy YN, Banerjee UC, Bhaumik J. Insights on the polypyrrole based nanoformulations for photodynamic therapy. J PORPHYR PHTHALOCYA 2021. [DOI: 10.1142/s1088424621300032] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
This review is written to endow updated information on polypyrrole based photosensitizers for the treatment of deadly diseases such as cancer and microbial infection. Tetrapyrrolic macromolecules such as porphyrins and phthalocyanines hold unique photophysical properties which make them very useful compounds for various biomedical applications. Besides their properties, they also have some limitations such as low water solubility, bioavailability, biocompatibility and lack of specificity, etc. Researchers are trying to overcome these limitations by incorporating photosensitizers into the different types of nanoparticles and improve the quality of photodynamic therapy. We have contributed to this field by synthesizing and developing polypyrrolic photosensitizer based nanoparticles for potential applications in antimicrobial and anticancer photodynamic activity. Throughout this review, newly synthesized and existing PSs conjugated/encapsulated/doped/incorporated with nanoparticles are emphasized, which are essential for current and future research themes. Also in this review, we briefly summarized the research work carried over the past few years by considering the porphyrin based photosensitizers as alternative therapeutic entities for the treatment of microbial infections, cancers, and many other diseases.
Collapse
Affiliation(s)
- Seema Kirar
- Department of Nanomaterials and Application Technology, Center of Innovative and Applied Bioprocessing (CIAB), Sector-81 (Knowledge City), S.A.S. Nagar-140306, Mohali, Punjab, India
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar-160062, Mohali, Punjab, India
| | - Neeraj Singh Thakur
- Department of Nanomaterials and Application Technology, Center of Innovative and Applied Bioprocessing (CIAB), Sector-81 (Knowledge City), S.A.S. Nagar-140306, Mohali, Punjab, India
- Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar-160062, Mohali, Punjab, India
| | - Yeddula Nikhileshwar Reddy
- Department of Nanomaterials and Application Technology, Center of Innovative and Applied Bioprocessing (CIAB), Sector-81 (Knowledge City), S.A.S. Nagar-140306, Mohali, Punjab, India
- Department of Chemical Sciences, Indian Institute of Science Education and Research (IISER), Sector-81, S.A.S. Nagar-140306, Mohali, Punjab, India
| | - Uttam Chand Banerjee
- Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar-160062, Mohali, Punjab, India
- Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar-160062, Mohali, Punjab, India
| | - Jayeeta Bhaumik
- Department of Nanomaterials and Application Technology, Center of Innovative and Applied Bioprocessing (CIAB), Sector-81 (Knowledge City), S.A.S. Nagar-140306, Mohali, Punjab, India
| |
Collapse
|
|
37
|
Photoinactivation of Pseudomonas aeruginosa Biofilm by Dicationic Diaryl-Porphyrin. Int J Mol Sci 2021; 22:ijms22136808. [PMID: 34202773 PMCID: PMC8269057 DOI: 10.3390/ijms22136808] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 06/21/2021] [Accepted: 06/22/2021] [Indexed: 12/17/2022] Open
Abstract
In recent years, antimicrobial photodynamic therapy (aPDT) has received increasing attention as a promising tool aimed at both treating microbial infections and sanitizing environments. Since biofilm formation on biological and inert surfaces makes difficult the eradication of bacterial communities, further studies are needed to investigate such tricky issue. In this work, a panel of 13 diaryl-porphyrins (neutral, mono- and di-cationic) was taken in consideration to photoinactivate Pseudomonas aeruginosa. Among cationic photosensitizers (PSs) able to efficiently bind cells, in this study two dicationic showed to be intrinsically toxic and were ruled out by further investigations. In particular, the dicationic porphyrin (P11) that was not toxic, showed a better photoinactivation rate than monocationic in suspended cells. Furthermore, it was very efficient in inhibiting the biofilms produced by the model microorganism Pseudomonas aeruginosa PAO1 and by clinical strains derived from urinary tract infection and cystic fibrosis patients. Since P. aeruginosa represents a target very difficult to inactivate, this study confirms the potential of dicationic diaryl-porphyrins as photo-activated antimicrobials in different applicative fields, from clinical to environmental ones.
Collapse
|
|
38
|
Fakih TM, Kurniawan F, Yusuf M, Mudasir M, Tjahjono DH. Molecular Dynamics of Cobalt Protoporphyrin Antagonism of the Cancer Suppressor REV-ERBβ. Molecules 2021; 26:3251. [PMID: 34071361 PMCID: PMC8198987 DOI: 10.3390/molecules26113251] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/15/2021] [Accepted: 05/26/2021] [Indexed: 11/17/2022] Open
Abstract
Nuclear receptor REV-ERBβ is an overexpressed oncoprotein that has been used as a target for cancer treatment. The metal-complex nature of its ligand, iron protoporphyrin IX (Heme), enables the REV-ERBβ to be used for multiple therapeutic modalities as a photonuclease, a photosensitizer, or a fluorescence imaging agent. The replacement of iron with cobalt as the metal center of protoporphyrin IX changes the ligand from an agonist to an antagonist of REV-ERBβ. The mechanism behind that phenomenon is still unclear, despite the availability of crystal structures of REV-ERBβ in complex with Heme and cobalt protoporphyrin IX (CoPP). This study used molecular dynamic simulations to compare the effects of REV-ERBβ binding to Heme and CoPP, respectively. The initial poses of Heme and CoPP in complex with agonist and antagonist forms of REV-ERBβ were predicted using molecular docking. The binding energies of each ligand were calculated using the MM/PBSA method. The computed binding affinity of Heme to REV-ERBβ was stronger than that of CoPP, in agreement with experimental results. CoPP altered the conformation of the ligand-binding site of REV-ERBβ, disrupting the binding site for nuclear receptor corepressor, which is required for REV-ERBβ to regulate the transcription of downstream target genes. Those results suggest that a subtle change in the metal center of porphyrin can change the behavior of porphyrin in cancer cell signaling. Therefore, modification of porphyrin-based agents for cancer therapy should be conducted carefully to avoid triggering unfavorable effects.
Collapse
Affiliation(s)
- Taufik Muhammad Fakih
- School of Pharmacy, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40135, Indonesia; (T.M.F.); (F.K.)
- Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Islam Bandung, Jalan Rangga Gading 8, Bandung 40116, Indonesia
| | - Fransiska Kurniawan
- School of Pharmacy, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40135, Indonesia; (T.M.F.); (F.K.)
| | - Muhammad Yusuf
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jalan Raya Bandung Sumedang Km 21, Sumedang 45363, Indonesia;
| | - Mudasir Mudasir
- Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara BLS 21, Yogyakarta 55281, Indonesia;
| | - Daryono Hadi Tjahjono
- School of Pharmacy, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40135, Indonesia; (T.M.F.); (F.K.)
| |
Collapse
|
|
39
|
Arutyunyan AF, Tevonyan LL, Beniaminov AD, Yegorov YE, Kaluzhny DN. The Phototoxic Effect of Water-Soluble Porphyrins on Human Clear Cell Renal Cell Carcinoma Line Сaki-1. Biophysics (Nagoya-shi) 2021. [DOI: 10.1134/s0006350921020020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
|
|
40
|
Nene LC, Sindelo A, Britton J, Nyokong T. Effect of ultrasonic frequency and power on the sonodynamic therapy activity of cationic Zn(II) phthalocyanines. J Inorg Biochem 2021; 217:111397. [PMID: 33611149 DOI: 10.1016/j.jinorgbio.2021.111397] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 02/03/2021] [Accepted: 02/05/2021] [Indexed: 01/03/2023]
Abstract
We report on the sonodynamic activity of cationic phthalocyanines (Pcs) and the effect of the variation of two parameters: ultrasound frequency and power (Par I (1 MHz, 1 W cm-2), Par II (1 MHz, 2 W cm-2), Par III (3 MHz, 1 W cm-2) and Par IV (3 MHz, 2 W cm-2)) on the efficiency of their reactive oxygen species generation and cancer eradication in vitro thereof. Where Par stands for the various combinations of these parameters. Four Pcs were investigated with substituents bearing diethylamine, ortho- and para-pyridine and morpholine groups. Overall, the para-pyridine and morpholine Pcs showed substantial sono-activity in the various ultrasound parameters with Par I and IV generally showing better singlet oxygen and hydroxyl radicals generation confirmed by electron paramagnetic resonance spectroscopy. In some cases, very high hydroxyl radicals' generation was observed at Par II. Furthermore, the fragmentation of the Pcs after Par II treatments was confirmed using UV-vis and magnetic circular dichroism spectroscopy. The reactive species generation efficacy decreased at Par III for all samples. Ultrasound assisted cytotoxicity of the Pcs was confirmed in vitro using the human (Michigan Cancer Foundation-7) breast cancer cell line.
Collapse
Affiliation(s)
- Lindokuhle Cindy Nene
- Institute for Nanotechnology Innovation, Rhodes University, Makhanda 6140, South Africa
| | - Azole Sindelo
- Institute for Nanotechnology Innovation, Rhodes University, Makhanda 6140, South Africa
| | - Jonathan Britton
- Institute for Nanotechnology Innovation, Rhodes University, Makhanda 6140, South Africa
| | - Tebello Nyokong
- Institute for Nanotechnology Innovation, Rhodes University, Makhanda 6140, South Africa.
| |
Collapse
|
|
41
|
Revuelta‐Maza MÁ, Heras E, Agut M, Nonell S, Torres T, Torre G. Self‐Assembled Binaphthyl‐Bridged Amphiphilic AABB Phthalocyanines: Nanostructures for Efficient Antimicrobial Photodynamic Therapy. Chemistry 2021; 27:4955-4963. [DOI: 10.1002/chem.202005060] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Revised: 01/02/2021] [Indexed: 12/17/2022]
Affiliation(s)
| | - Elena Heras
- Institut Químic de Sarrià Universitat Ramon Llull 08017 Barcelona Spain
| | - Montserrat Agut
- Institut Químic de Sarrià Universitat Ramon Llull 08017 Barcelona Spain
| | - Santi Nonell
- Institut Químic de Sarrià Universitat Ramon Llull 08017 Barcelona Spain
| | - Tomás Torres
- Universidad Autónoma de Madrid C/ Francisco Tomás y Valiente 7 28049 Madrid Spain
- Institute for Advanced Research in Chemical Sciences (IAdChem) Universidad Autónoma de Madrid 28049 Madrid Spain
- Instituto Madrileño de Estudios Avanzados (IMDEA)-Nanociencia C/ Faraday 9 Cantoblanco 28049, Madrid Spain
| | - Gema Torre
- Universidad Autónoma de Madrid C/ Francisco Tomás y Valiente 7 28049 Madrid Spain
- Institute for Advanced Research in Chemical Sciences (IAdChem) Universidad Autónoma de Madrid 28049 Madrid Spain
| |
Collapse
|
|
42
|
Xie Q, Su M, Liu Y, Zhang D, Li Z, Bai M. Translocator protein (TSPO)-Targeted agents for photodynamic therapy of cancer. Photodiagnosis Photodyn Ther 2021; 34:102209. [PMID: 33561573 DOI: 10.1016/j.pdpdt.2021.102209] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 01/15/2021] [Accepted: 02/01/2021] [Indexed: 11/26/2022]
Abstract
Photodynamic therapy (PDT) is a clinically approved therapeutic strategy that combines a specific wavelength of light and light-activated photosensitizers (PSs). The usage of PDT for cancer treatment is often hampered by the lack of tumor selectivity of PSs, which may cause photodamage to surrounding normal tissues. Recently, translocator protein (TSPO) has attracted great interest as a tumor biomarker, whose expression correlates with tumor aggressiveness. In this study, we report the development of a series of novel TSPO-PSs based on quinazoline, pyrazolopyrimidine, and tetrahydrocarbazole structures. These TSPO-PSs bind to TSPO with nanomolar affinities and demonstrated efficient and target-specific PDT effect upon light irradiation. Therefore, they may have great potential in the treatment of tumors associated with high-TSPO expression.
Collapse
Affiliation(s)
- Qing Xie
- Vanderbilt University Institute of Imaging Sciences, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN, 37232, USA
| | - Meng Su
- Vanderbilt University Institute of Imaging Sciences, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN, 37232, USA
| | - Yang Liu
- Vanderbilt University Institute of Imaging Sciences, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN, 37232, USA
| | - Dawei Zhang
- Vanderbilt University Institute of Imaging Sciences, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN, 37232, USA; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Guangzhou Medical University, No. 250 East Changgang Road, Guangzhou, 510260, PR China
| | - Zhen Li
- Vanderbilt University Institute of Imaging Sciences, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN, 37232, USA; Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, No. 4 Chongshan East Road, Huanggu District, Shenyang, 110032, PR China
| | - Mingfeng Bai
- Vanderbilt University Institute of Imaging Sciences, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN, 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
| |
Collapse
|
|
43
|
Tumor-selective new piperazine-fragmented silicon phthalocyanines initiate cell death in breast cancer cell lines. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2021; 216:112143. [PMID: 33550219 DOI: 10.1016/j.jphotobiol.2021.112143] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 01/22/2021] [Accepted: 01/26/2021] [Indexed: 02/08/2023]
Abstract
A new silicon phthalocyanine with piperazine-furan ring and its quaternized form were synthesized. All compounds were analyzed by spectroscopic techniques (FT-IR, 1H-NMR, MS, and UV-vis), and the absorbance characteristics of silicon phthalocyanines were evaluated with the expected strong typical absorption bands in the far-red spectrum. The cytotoxic effects of these phthalocyanines induced by photodynamic therapy (PDT) were determined in a dose-dependent manner. Following cytotoxicity analysis, flow cytometric research of cell death was performed. The formation of reactive oxygen species (ROS) was determined by confocal microscopy. High levels of cytotoxicity and decreased viable cell population have been detected in cancer cells after treatment. In addition, ROS formation was observed in PDT treated cancer cells. However, low levels of cell death and ROS formation were observed in non-tumorigenic cells. According to western blot data, PDT-mediated treatment was found to provide different expression patterns of the cleaved PARP1 protein. The presented study demonstrates that PDT-mediated treatment of newly synthesized phthalocyanines has significant anti-cancer effects on breast cancer cells and may induce different cell death pathways.
Collapse
|
|
44
|
Castro KADF, Costa LD, Prandini JA, Biazzotto JC, Tomé AC, Hamblin MR, da Graça P M S Neves M, Faustino MAF, da Silva RS. The Photosensitizing Efficacy of Micelles Containing a Porphyrinic Photosensitizer and KI against Resistant Melanoma Cells. Chemistry 2021; 27:1990-1994. [PMID: 33185284 PMCID: PMC7921759 DOI: 10.1002/chem.202004389] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 11/05/2020] [Indexed: 11/07/2022]
Abstract
Photodynamic therapy (PDT) is a promising alternative to overcome the resistance of melanoma to conventional therapies. Currently applied photosensitizers (PS) are often based on tetrapyrrolic macrocycles like porphyrins. Unfortunately, in some cases the use of this type of derivative is limited due to their poor solubility in the biological environment. Feasible approaches to surpass this drawback are based on lipid formulations. Besides that, and inspired in the efficacy of potassium iodide (KI) for antimicrobial photodynamic therapy (aPDT), the combined effect of singlet oxygen (1 O2 ) with KI was assessed in this work, as an alternative strategy to potentiate the effect of PDT against resistant melanoma cells.
Collapse
Affiliation(s)
- Kelly A D F Castro
- Department of Physics and Chemistry, Faculty of, Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal
| | - Letícia D Costa
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal
| | - Juliana A Prandini
- Department of Physics and Chemistry, Faculty of, Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Juliana C Biazzotto
- Department of Physics and Chemistry, Faculty of, Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Augusto C Tomé
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, 2028, South Africa
| | | | - M Amparo F Faustino
- LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, Aveiro, Portugal
| | - Roberto S da Silva
- Department of Physics and Chemistry, Faculty of, Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| |
Collapse
|
|
45
|
Sharma D, Mazumder ZH, Sengupta D, Mukherjee A, Sengupta M, Das RK, Barbhuiya MH, Palit P, Jha T. Cancer photocytotoxicity and anti-inflammatory response of cis-A2B2 type meso-p-nitrophenyl and p-hydroxyphenyl porphyrin and its zinc(ii) complex: a synthetic alternative to the THPP synthon. NEW J CHEM 2021. [DOI: 10.1039/d0nj05106c] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
In comparison with the popular synthetic synthon THPP, the cis-A2B2 type of porphyrin derivative and its zinc(ii) complex PN2(OH)2Zn offer more promising photochemical and photobiological outcomes.
Collapse
Affiliation(s)
| | | | | | - Avinaba Mukherjee
- Department of Zoology
- Charuchandra College
- University of Calcutta
- Kolkata
- India
| | | | | | | | - Partha Palit
- Department of Pharmaceutical Sciences
- Assam University
- Silchar
- India
| | - Tarun Jha
- Department of Pharmaceutical Technology
- Jadavpur University
- Kolkata
- India
| |
Collapse
|
|
46
|
Babu B, Mack J, Nyokong T. A heavy-atom-free π-extended N-confused porphyrin as a photosensitizer for photodynamic therapy. NEW J CHEM 2021. [DOI: 10.1039/d1nj00112d] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
A heavy-atom-free π-extended N-confused porphyrin is reported that is suitable for use as a photosensitizer for photodynamic therapy in both the green region and therapeutic window.
Collapse
Affiliation(s)
- Balaji Babu
- Institute for Nanotechnology Innovation
- Department of Chemistry
- Rhodes University
- Makhanda
- South Africa
| | - John Mack
- Institute for Nanotechnology Innovation
- Department of Chemistry
- Rhodes University
- Makhanda
- South Africa
| | - Tebello Nyokong
- Institute for Nanotechnology Innovation
- Department of Chemistry
- Rhodes University
- Makhanda
- South Africa
| |
Collapse
|
|
47
|
Openda YI, Ngoy BP, Muya JT, Nyokong T. Synthesis, theoretical calculations and laser flash photolysis studies of selected amphiphilic porphyrin derivatives used as biofilm photodegradative materials. NEW J CHEM 2021. [DOI: 10.1039/d1nj02651h] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Two positively charged metalloporphyrins were synthesized and theoretical studies were carried out. The complexes efficiently eradicated S. aureus and E. coli bacterial cells at 415 nm.
Collapse
Affiliation(s)
- Yolande Ikala Openda
- Institute for Nanotechnology Innovation, Department of Chemistry, Rhodes University, Makhanda 6140, South Africa
| | - Bokolombe Pitchou Ngoy
- Institute for Nanotechnology Innovation, Department of Chemistry, Rhodes University, Makhanda 6140, South Africa
- Département de Chimie, Université de Kinshasa, Kinshasa, Democratic Republic of the Congo
| | - Jules Tshishimbi Muya
- Département de Chimie, Université de Kinshasa, Kinshasa, Democratic Republic of the Congo
| | - Tebello Nyokong
- Institute for Nanotechnology Innovation, Department of Chemistry, Rhodes University, Makhanda 6140, South Africa
| |
Collapse
|
|
48
|
Mazumder ZH, Sharma D, Sengupta D, Mukherjee A, Boruah JS, Basu S, Shukla PK, Jha T. Photodynamic activity attained through the ruptured π-conjugation of pyridyl groups with a porphyrin macrocycle: synthesis and the photophysical and photobiological evaluation of 5-mono-(4-nitrophenyl)-10,15,20-tris-[4-(phenoxymethyl)pyridine]-porphyrin and its Zn(ii) complex. Photochem Photobiol Sci 2020; 19:1776-1789. [PMID: 33320165 DOI: 10.1039/d0pp00319k] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
This article compares a reported hydrophobic and photobiologically inert porphyrin synthon, (NPh)TPyP, bearing a single meso-4-nitrophenyl group and three meso-pyridyl groups (A3B type) with a new photobiologically active metal-free porphyrin, P3N, and its zinc-complex, P3NZn, which bear a meso-4-nitrophenyl group along with three distal pyridyl groups. Both P3N and P3NZn experience ruptured π-conjugation with the porphyrin macrocycle and attain hydrophilicity, as indicated via density functional theory (DFT) calculations, becoming photobiologically active under in vitro conditions. The non-invasive photodynamic activity (PDA) predominantly shown by the zinc-complex P3NZn (with higher hydrophilicity) towards KRAS-mutated human lung-cancer cells (A549) was studied. The results indicate the existence of intracellular singlet oxygen inflicted anticancer PDA, which is apparent through the upregulation of intracellular reactive oxygen species (ROS) and the downregulation of both intracellular superoxide dismutase (SOD) and intracellular reduced glutathione (GSH) levels. The trends obtained from both SOD and GSH assays were indicators of therapeutic defence against oxidative stress via neutralizing superoxide anions (SOA).
Collapse
Affiliation(s)
- Zeaul H Mazumder
- Department of Chemistry, Assam University, Silchar, Assam 788011, India.
| | | | | | | | | | | | | | | |
Collapse
|
|
49
|
Wang X, Shi Z, Chen H, Huang F. Nanoscale integration of porphyrin in GroEL protein cage: Photophysical and photochemical investigation. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2020; 240:118596. [PMID: 32599481 DOI: 10.1016/j.saa.2020.118596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 06/02/2020] [Accepted: 06/06/2020] [Indexed: 06/11/2023]
Abstract
In this paper, we introduce a new type of functional, supramolecular porphyrin conjugate created using the bacterial GroEL protein cage based on non-specific hydrophobic interaction. The synthesis, structure and property of the porphyrin conjugate were characterized by dynamic light scattering, UV-vis spectroscopy and fluorescence spectroscopy. We observed that the model zinc-tetraphenylporphyrin (Zn-TPP) with high hydrophobicity can be well-dispersed in aqueous solutions with the aid of GroEL open chamber, which is known to be a favorable nanocompartment for aggregation-prone molecules. The maximal encapsulation efficiency of Zn-TPP in GroEL was determined to be ~98%. It is further seen that the constructed double Zn-TPP-GroEL complex exhibited good photocatalytic activity in the model reactions of the production of singlet oxygen and the reduction of methyl viologen under illumination with visible light. Moreover, we found that GroEL can significantly improve the photostability of Zn-TPP molecules as a result of nanoscale assembly within its hydrophobic chamber. Hence enhanced water solubility and photostability of Zn-TPP, which are considered as the first two hurdles for the wide usage of porphyrins, were achieved simultaneously by the development of GroEL cage as a building block. Supramolecular nanostructures formed from porphyrins (or related molecules) and GroEL for photocatalysis would greatly simplify applications of such structures.
Collapse
Affiliation(s)
- Xiaoqiang Wang
- State Key Laboratory of Heavy Oil Processing, College of Chemical Engineering, China University of Petroleum (East China), 66 West Changjiang Road, Qingdao, Shandong 266580, PR China.
| | - Zhuang Shi
- State Key Laboratory of Heavy Oil Processing, College of Chemical Engineering, China University of Petroleum (East China), 66 West Changjiang Road, Qingdao, Shandong 266580, PR China
| | - Han Chen
- State Key Laboratory of Heavy Oil Processing, College of Chemical Engineering, China University of Petroleum (East China), 66 West Changjiang Road, Qingdao, Shandong 266580, PR China
| | - Fang Huang
- State Key Laboratory of Heavy Oil Processing, College of Chemical Engineering, China University of Petroleum (East China), 66 West Changjiang Road, Qingdao, Shandong 266580, PR China.
| |
Collapse
|
|
50
|
Mazumdar ZH, Sharma D, Mukherjee A, Basu S, Shukla PK, Jha T, Sengupta D. meso-Thiophenium Porphyrins and Their Zn(II) Complexes: A New Category of Cationic Photosensitizers. ACS Med Chem Lett 2020; 11:2041-2047. [PMID: 33062190 DOI: 10.1021/acsmedchemlett.0c00266] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 09/10/2020] [Indexed: 12/15/2022] Open
Abstract
A new category of cationic meso-thiophenium porphyrins are introduced as possible alternatives to the popular meso-pyridinium porphyrins. Combinations of cationic porphyrins bearing meso-2-methylthiophenium and meso-4-hydroxyphenyl moieties T2(OH)2M (A2B2 type) and T(OH)3M (AB3 type) along with their zinc(II) complexes T2(OH)2MZn and T(OH)3MZn, are reported. The increase in the number of thienyl groups attached to the meso-positions of the porphyrin derivatives (A2B2 frame) has been shown to impart longer fluorescence lifetimes and stronger photocytotoxicity toward A549 lung cancer cells, as evident with T2(OH)2M and its corresponding diamagnetic metal complex T2(OH)2MZn. The photoactivated T2(OH)2MZn imparts an early stage reactive oxygen species (ROS) upregulation and antioxidant depletion in A549 cells and contributes to the strongest oxidative stress-induced cell death mechanism in the series. The DFT calculations of the singlet-triplet energy gap (ΔE) of all the four hydrophilic thiophenium porphyrin derivatives establish the potential applicability of these cationic photosensitizers as PDT agents.
Collapse
Affiliation(s)
- Zeaul Hoque Mazumdar
- Department of Chemistry, Assam University, Dargakona, Silchar-788011, Assam India
| | - Debdulal Sharma
- Department of Chemistry, Assam University, Dargakona, Silchar-788011, Assam India
| | - Avinaba Mukherjee
- Department of Zoology, Charuchandra College, University of Calcutta, Kolkata-700029, West Bengal, India
| | - Samita Basu
- Chemical Science Division Saha, Institute of Nuclear Physics, Kolkata-700064, West Bengal, India
| | - Pradeep Kumar Shukla
- Department of Physics, Assam University, Dargakona, Silchar-788011, Assam, India
| | - Tarun Jha
- Department of Pharmaceutical Technology, Jadavpur University, Kolkata-700032, West Bengal, India
| | - Devashish Sengupta
- Department of Chemistry, Assam University, Dargakona, Silchar-788011, Assam India
| |
Collapse
|