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1
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Winslow M, Hazelby A, Robinson D. Spin-Restricted Descriptions of Singlet Oxygen Reactions from XMS-CASPT2 Benchmarks. J Phys Chem A 2024; 128:4128-4137. [PMID: 38739627 PMCID: PMC11129307 DOI: 10.1021/acs.jpca.4c00744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 04/25/2024] [Accepted: 05/01/2024] [Indexed: 05/16/2024]
Abstract
Reactions of singlet oxygen are numerous, some of which are desired but many are unwanted. Therefore, the ability to correctly predict and interpret this reactivity for complex molecular systems is essential to our understanding of singlet oxygen reactions. DFT is widely used for predicting many reactions but is not suited to degenerate electronic structures; application to isolated singlet oxygen often uses the spin-unrestricted formalism, which results in severe spin contamination. In this work, we demonstrate that spin-restricted DFT can correctly describe the reaction pathway for four prototypical singlet oxygen reactions. By careful benchmarking with XMS-CASPT2, we show that, from the first transition state onward, the degeneracy of the 1Δg state is broken due to differing interactions of the (degenerate) π* orbitals with the organic substrate; this result is well replicated with DFT. These findings demonstrate the utility of using spin-restricted DFT to explore reactions, opening the way to confidently use this computationally efficient method for molecular systems of medium to large organic molecules.
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Affiliation(s)
| | - Alexander Hazelby
- Department of Chemistry and
Forensics, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United
Kingdom
| | - David Robinson
- Department of Chemistry and
Forensics, School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United
Kingdom
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2
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Xu X, Liu A, Liu S, Ma Y, Zhang X, Zhang M, Zhao J, Sun S, Sun X. Application of molecular dynamics simulation in self-assembled cancer nanomedicine. Biomater Res 2023; 27:39. [PMID: 37143168 PMCID: PMC10161522 DOI: 10.1186/s40824-023-00386-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 04/21/2023] [Indexed: 05/06/2023] Open
Abstract
Self-assembled nanomedicine holds great potential in cancer theragnostic. The structures and dynamics of nanomedicine can be affected by a variety of non-covalent interactions, so it is essential to ensure the self-assembly process at atomic level. Molecular dynamics (MD) simulation is a key technology to link microcosm and macroscale. Along with the rapid development of computational power and simulation methods, scientists could simulate the specific process of intermolecular interactions. Thus, some experimental observations could be explained at microscopic level and the nanomedicine synthesis process would have traces to follow. This review not only outlines the concept, basic principle, and the parameter setting of MD simulation, but also highlights the recent progress in MD simulation for self-assembled cancer nanomedicine. In addition, the physicochemical parameters of self-assembly structure and interaction between various assembled molecules under MD simulation are also discussed. Therefore, this review will help advanced and novice researchers to quickly zoom in on fundamental information and gather some thought-provoking ideas to advance this subfield of self-assembled cancer nanomedicine.
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Affiliation(s)
- Xueli Xu
- School of Science, Shandong Jianzhu University, Jinan, 250101, China
| | - Ao Liu
- School of Science, Shandong Jianzhu University, Jinan, 250101, China
| | - Shuangqing Liu
- School of Chemistry and Pharmaceutical Engineering, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China
| | - Yanling Ma
- School of Chemistry and Pharmaceutical Engineering, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China
| | - Xinyu Zhang
- School of Chemistry and Pharmaceutical Engineering, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China
| | - Meng Zhang
- School of Chemistry and Pharmaceutical Engineering, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China
| | - Jinhua Zhao
- School of Science, Shandong Jianzhu University, Jinan, 250101, China
| | - Shuo Sun
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, 02115, USA
| | - Xiao Sun
- School of Chemistry and Pharmaceutical Engineering, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250000, China.
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3
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Aung W, Tsuji AB, Hanaoka K, Higashi T. Folate receptor-targeted near-infrared photodynamic therapy for folate receptor-overexpressing tumors. World J Clin Oncol 2022; 13:880-895. [PMID: 36483974 PMCID: PMC9724186 DOI: 10.5306/wjco.v13.i11.880] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/12/2022] [Accepted: 10/18/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Photodynamic therapy (PDT) is a minimally invasive form of cancer therapy, and the development of a novel photosensitizer (PS) with optimal properties is important for enhancing PDT efficacy. Folate receptor (FR) membrane protein is frequently overexpressed in 40% of human cancer and a good candidate for tumor-specific targeting. Specific active targeting of PS to FR can be achieved by conjugation with the folate moiety. A folate-linked, near-infrared (NIR)-sensitive probe, folate-Si-rhodamine-1 (FolateSiR-1), was previously developed and is expected to be applicable to NIR-PDT.
AIM To investigate the therapeutic efficacy of NIR-PDT induced by FolateSiR-1, a FR-targeted PS, in preclinical cancer models.
METHODS FolateSiR-1 was developed by conjugating a folate moiety to the Si-rhodamine derivative through a negatively charged tripeptide linker. FR expression in the designated cell lines was examined by western blotting (WB). The selective binding of FolateSiR-1 to FR was confirmed in FR overexpressing KB cells (FR+) and tumors by fluorescence microscopy and in vivo fluorescence imaging. Low FR expressing OVCAR-3 and A4 cell lines were used as negative controls (FR-). The NIR light (635 ± 3 nm)-induced phototoxic effect of FolateSiR-1 was evaluated by cell viability imaging assays. The time-dependent distribution of FolateSiR-1 and its specific accumulation in KB tumors was determined using in vivo longitudinal fluorescence imaging. The PDT effect of FolateSiR-1 was evaluated in KB tumor-bearing mice divided into four experimental groups: (1) FolateSiR-1 (100 μmol/L) alone; (2) FolateSiR-1 (100 μmol/L) followed by NIR irradiation (50 J/cm2); (3) NIR irradiation (50 J/cm2) alone; and (4) no treatment. Tumor volume measurement and immunohistochemical (IHC) and histological examinations of the tumors were performed to analyze the effect of PDT.
RESULTS High FR expression was observed in the KB cells by WB, but not in the OVCAR-3 and A4 cells. Substantial FR-specific binding of FolateSiR-1 was observed by in vitro and in vivo fluorescence imaging. Cell viability imaging assays showed that NIR-PDT induced cell death in KB cells. In vivo longitudinal fluorescence imaging showed rapid peak accumulation of FolateSiR-1 in the KB tumors 2 h after injection. In vivo PDT conducted at this time point caused tumor growth delay. The relative tumor volumes in the PDT group were significantly reduced compared to those in the other groups [5.81 ± 1.74 (NIR-PDT) vs 12.24 ± 2.48 (Folate-SiR-1), vs 11.84 ± 3.67 (IR), vs 12.98 ± 2.78 (Untreated), at Day 16, P < 0.05]. IHC analysis revealed reduced proliferation marker Ki-67-positive cells in the PDT treated tumors, and hematoxylin-eosin staining revealed features of necrotic- and apoptotic cell death.
CONCLUSION FolateSiR-1 has potential for use in PDT, and FR-targeted NIR-PDT may open a new effective strategy for the treatment of FR-overexpressing tumors.
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Affiliation(s)
- Winn Aung
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological 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 and Radiological Science and Technology, Chiba 263-8555, Japan
| | - Kenjiro Hanaoka
- Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan
| | - Tatsuya Higashi
- Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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4
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Shi L, Zhang P, Liu X, Li Y, Wu W, Gao X, Liu B. An Activity-Based Photosensitizer to Reverse Hypoxia and Oxidative Resistance for Tumor Photodynamic Eradication. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2022; 34:e2206659. [PMID: 36106613 DOI: 10.1002/adma.202206659] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 09/12/2022] [Indexed: 06/15/2023]
Abstract
Photodynamic therapy (PDT) has been a well-accepted clinical treatment for malignant tumors owing to its noninvasiveness and high spatiotemporal selectivity. However, the treatment outcome of current PDT applications is hindered by hypoxia and intracellular oxidative resistance of solid tumors. Recent studies have shown that inhibiting histone deacetylases (HDACs) can induce cell ferroptosis, reverse hypoxia, and elevate oxidative status. Theoretically, the design and synthesis of activity-based photosensitizers that target HDACs can address the bottlenecks of PDT. Herein, the concept of an activity-based photosensitizer is presented for targeting HDACs, which is designed based on a quinoxalinone scaffold through a pharmacophore migration strategy. The developed activity-based photosensitizer can inhibit HDACs, and overcome hypoxia and intracellular oxidative resistance, realizing the full potential of photosensitizers for malignant tumor treatment. The molecular design strategy proposed in this project should provide theoretical guidance for the development of ideal photosensitizers for practical applications.
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Affiliation(s)
- Leilei Shi
- Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore
- The Eighth Affiliated Hospital, Sun Yat-sen University, 3025 Shennan Middle Road, Shenzhen, 518000, China
| | - Peng Zhang
- Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, 47 Youyi Road, Shenzhen, 518001, China
| | - Xiaoxiao Liu
- Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, 131 Dong An Road, Shanghai, 200032, China
| | - Yuzhen Li
- The Eighth Affiliated Hospital, Sun Yat-sen University, 3025 Shennan Middle Road, Shenzhen, 518000, China
| | - Wenbo Wu
- Institute of Molecular Aggregation Science, Tianjin University, 92 Weijin Road, Tianjin, 300072, China
| | - Xihui Gao
- Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, 131 Dong An Road, Shanghai, 200032, China
| | - Bin Liu
- Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117585, Singapore
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5
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From Intestinal Epithelial Homeostasis to Colorectal Cancer: Autophagy Regulation in Cellular Stress. Antioxidants (Basel) 2022; 11:antiox11071308. [PMID: 35883800 PMCID: PMC9311735 DOI: 10.3390/antiox11071308] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 06/24/2022] [Accepted: 06/27/2022] [Indexed: 02/01/2023] Open
Abstract
The intestinal epithelium is continuously exposed to abundant stress stimuli, which relies on an evolutionarily conserved process, autophagy, to maintain its homeostasis by degrading and recycling unwanted and damaged intracellular substances. Otherwise, disruption of this balance will result in the development of a wide range of disorders, including colorectal cancer (CRC). Dysregulated autophagy is implicated in the regulation of cellular responses to stress during the development, progression, and treatment of CRC. However, experimental investigations addressing the impact of autophagy in different phases of CRC have generated conflicting results, showing that autophagy is context-dependently related to CRC. Thus, both inhibition and activation of autophagy have been proposed as therapeutic strategies against CRC. Here, we will discuss the multifaceted role of autophagy in intestinal homeostasis and CRC, which may provide insights for future research directions.
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6
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Real-time imaging mitochondrial viscosity dynamic during mitophagy mediated by photodynamic therapy. Anal Chim Acta 2021; 1178:338847. [PMID: 34482880 DOI: 10.1016/j.aca.2021.338847] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 07/07/2021] [Accepted: 07/08/2021] [Indexed: 01/10/2023]
Abstract
Photodynamic therapy has been generally developed and approved as a promising theranostic technique in recent years, which requires photosensitizers to bear high efficiency of reactive oxygen species production, precisely targeting ability and excellent biocompatibility. The real-time monitoring the microenvironments such as viscosity dynamic involved in mitophagy mediated by photodynamic therapy is significantly important to understand therapeutic process but barely reported. In this work, a pyridinium-functionalized triphenylamine derivative, (E)-4-(2-(4'-(diphenylamino)-[1,1'-biphenyl]-4-yl)vinyl)-1-methylpyridin-1-ium iodide (Mito-I), was exploited as photosensitizer for mitochondria-targeted photodynamic therapy and as fluorescent probe for imaging the mitochondrial viscosity dynamic during mitophagy simultaneously. The results indicated that the additional phenyl ring in Mito-I was beneficial to promote its efficiency of singlet oxygen production. The excellent capability of targeting mitochondria and singlet oxygen generation allowed Mito-I for the specifically mitochondria-targeted photodynamic therapy. Moreover, Mito-I displayed off-on fluorescence response to viscosity with high selectivity and sensitivity. The observed enhancement in fluorescence intensity of Mito-I revealed the increasingly mitochondrial viscosity during mitophagy mediated by the photodynamic therapy of Mito-I. As a result, this work presents a rare example to realize the mitochondria-targeting photodynamic therapy as well as the real-time monitoring viscosity dynamic during mitophagy, which is of great importance for the basic medical research involved in photodynamic therapy.
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7
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Rodrigues CV, Johnson KR, Lombardi VC, Rodrigues MO, Sobrinho JA, de Bettencourt-Dias A. Photocytotoxicity of Thiophene- and Bithiophene-Dipicolinato Luminescent Lanthanide Complexes. J Med Chem 2021; 64:7724-7734. [PMID: 34018753 DOI: 10.1021/acs.jmedchem.0c01805] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
New thiophene-dipicolinato-based compounds, K2nTdpa (n = 1, 2), were isolated. Their anions are sensitizers of lanthanide ion (LnIII) luminescence and singlet oxygen generation (1O2). Emission in the visible and near-infrared regions was observed for the LnIII complexes with efficiencies (ϕLn) ϕEu = 33% and ϕYb = 0.31% for 1Tdpa2- and ϕYb = 0.07% for 2Tdpa2-. The latter does not sensitize EuIII emission. Fluorescence imaging of HeLa live cells incubated with K3[Eu(1Tdpa)3] indicates that the complex permeates the cell membrane and localizes in the mitochondria. All complexes generate 1O2 in solution with efficiencies (ϕO12) as high as 13 and 23% for the GdIII complexes of 1Tdpa2- and 2Tdpa2-, respectively. [Ln(nTdpa)3]3- (n = 1, 2) are phototoxic to HeLa cells when irradiated with UV light with IC50 values as low as 4.2 μM for [Gd(2Tdpa)3]3- and 91.8 μM for [Eu(1Tdpa)3]3-. Flow cytometric analyses indicate both apoptotic and necrotic cell death pathways.
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Affiliation(s)
- Carime V Rodrigues
- Department of Chemistry, University of Nevada, Reno, Reno, Nevada 89557, United States.,Laboratório de Inorgânica e Materiais, Instituto de Química, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasilia 70910-900 DF, Brazil
| | - Katherine R Johnson
- Department of Chemistry, University of Nevada, Reno, Reno, Nevada 89557, United States
| | - Vincent C Lombardi
- Department of Microbiology and Immunology, University of Nevada, Reno, Reno, Nevada 89557, United States
| | - Marcelo O Rodrigues
- Laboratório de Inorgânica e Materiais, Instituto de Química, Universidade de Brasília, Campus Universitário Darcy Ribeiro, Brasilia 70910-900 DF, Brazil
| | - Josiane A Sobrinho
- Department of Chemistry, University of Nevada, Reno, Reno, Nevada 89557, United States
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8
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Zhu T, Shi L, Ma C, Xu L, Yang J, Zhou G, Zhu X, Shen L. Fluorinated chitosan-mediated intracellular catalase delivery for enhanced photodynamic therapy of oral cancer. Biomater Sci 2021; 9:658-662. [PMID: 33463639 DOI: 10.1039/d0bm01898h] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
A pH-responsive fluorinated chitosan-chlorin e6 (FC-Ce6) was employed here for the intracellular delivery of catalase to relieve the hypoxic micro-environment. Upon simple mixing, FC-Ce6 and catalase co-assemble to form stable nanoparticles, which show a greatly improved cross-membrane penetration capacity compared with catalase alone or nonfluorinated CS-Ce6/catalase nanoparticles. Under catalase catalysis, a high concentration of intracellular H2O2 can be transformed into O2. Upon irradiation, due to the continuous formation of cytotoxic singlet oxygen (1O2), our nanoparticles showed superior anti-cancer activity in contrast to free Ce6 and nonfluorinated CS-Ce6/catalase nanoparticles. Our study proposes an effective intracellular catalase delivery system to overcome hypoxia for enhanced PDT against oral cancer.
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Affiliation(s)
- Ting Zhu
- Department of Oral & Maxillofacial-Head & Neck Oncology, Department of Laser and Aesthetic Medicine, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China.
| | - Leilei Shi
- School of Chemistry and Chemical Engineering, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Chuan Ma
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China
| | - Li Xu
- School of Chemistry and Chemical Engineering, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Jiapei Yang
- School of Chemistry and Chemical Engineering, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Guoyu Zhou
- Department of Oral & Maxillofacial-Head & Neck Oncology, Department of Laser and Aesthetic Medicine, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China.
| | - Xinyuan Zhu
- School of Chemistry and Chemical Engineering, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Lingyue Shen
- Department of Oral & Maxillofacial-Head & Neck Oncology, Department of Laser and Aesthetic Medicine, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China.
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Yan S, Tang D, Hong Z, Wang J, Yao H, Lu L, Yi H, Fu S, Zheng C, He G, Zou H, Hou X, He Q, Xiong L, Li Q, Deng X. CD133 peptide-conjugated pyropheophorbide-a as a novel photosensitizer for targeted photodynamic therapy in colorectal cancer stem cells. Biomater Sci 2021; 9:2020-2031. [PMID: 33439161 DOI: 10.1039/d0bm01874k] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Colorectal cancer (CRC) is the third most common cancer around the world. Recent findings suggest that cancer stem cells (CSCs) play a pivotal role in the resistance to current therapeutic modalities, including surgery and chemotherapy. Photodynamic therapy (PDT) is a promising non-invasive therapeutic strategy for advanced metastatic CRC. Traditional photosensitizers such as pyropheophorbide-a (Pyro) lack tumor selectivity, causing unwanted treatment-related toxicity to the surrounding normal tissue. In order to enhance the targeting properties of Pyro, we synthesize a novel photosensitizer, CD133-Pyro, via the conjugation of Pyro to a peptide domain targeting CD133, which is highly expressed on CRC CSCs and correlated with poor prognosis of CRC patients. We demonstrate that CD133-Pyro possesses the targeted delivery capacity both in CRC CSCs derived from HT29 and SW620 cell lines and in a xenograft mouse model of tumor growth. CD133-Pyro PDT can promote the production of reactive oxygen species (ROS), suppress the stemness properties, and induce autophagic cell death in CRC CSCs. Furthermore, CD133-Pyro PDT has a potent inhibitory effect on CRC CSC-derived xenograft tumors in nude mice. These findings may offer a useful and important strategy for the treatment of CRC through targeting CSCs.
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Affiliation(s)
- Shichao Yan
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
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10
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Zhang P, Kuang H, Xu Y, Shi L, Cao W, Zhu K, Xu L, Ma J. Rational Design of a High-Performance Quinoxalinone-Based AIE Photosensitizer for Image-Guided Photodynamic Therapy. ACS APPLIED MATERIALS & INTERFACES 2020; 12:42551-42557. [PMID: 32862640 DOI: 10.1021/acsami.0c12670] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Because light exhibits excellent spatiotemporal resolution, photodynamic therapy (PDT) is becoming a promising method for cancer treatment. However, in a single photosensitizer (PS), it remains a big challenge to achieve all key properties including effective singlet oxygen (1O2) production under long-wavelength laser and bright near-infrared (NIR) emission without toxicity in the dark. In addition, clinically used traditional PSs encounter quenched fluorescence and decreased 1O2 production because of molecular aggregation in aqueous solution. To solve the aforementioned issues, quinoxalinone CN (QCN) with effective 1O2 generation under long-wavelength (530 nm) laser irradiation and aggregation-induced NIR emission is rationally designed by precise optimization of the quinoxalinone scaffold. After being encapsulated by an amphiphilic polymer (DSPE-PEG), the yielded nanoparticles exhibit highly efficient 1O2 production and stable NIR fluorescence located at 800 nm without obvious toxicity under the dark. Both in vitro and in vivo evaluation identify that QCN would be a promising PS for image-guided PDT of tumors.
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Affiliation(s)
- Peng Zhang
- Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen 518001, China
| | - Haizhu Kuang
- Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen 518001, China
| | - Yingying Xu
- Department of Pharmaceutics, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China
| | - Leilei Shi
- School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
| | - Weiling Cao
- Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen 518001, China
| | - Kongkai Zhu
- School of Biological Science and Technology, University of Jinan, Jinan 250022, China
| | - Li Xu
- School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
| | - Jing Ma
- The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong 518003, China
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11
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Shi L, Hu F, Duan Y, Wu W, Dong J, Meng X, Zhu X, Liu B. Hybrid Nanospheres to Overcome Hypoxia and Intrinsic Oxidative Resistance for Enhanced Photodynamic Therapy. ACS NANO 2020; 14:2183-2190. [PMID: 32023035 DOI: 10.1021/acsnano.9b09032] [Citation(s) in RCA: 124] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
Photodynamic therapy (PDT) has been a well-accepted clinical treatment for malignant tumors owing to its noninvasiveness and high spatiotemporal selectivity. However, the efficiency of PDT is still severely hindered by an inherent aggregation-caused quenching (ACQ) effect of traditional photosensitizers (PSs), the presence of B-cell lymphoma 2 (Bcl-2), an antiapoptosis protein in cells, and hypoxia in the tumor microenvironment. To address these issues, hybrid nanospheres containing Fe3+, aggregation-induced emission (AIE) PS, and Bcl-2 inhibitor of sabutoclax were constructed via coordination-driven self-assembly in aqueous media. Once the hybrid nanospheres are taken up by tumor cells, intracellular O2 concentration is observed to increase via Fenton reaction driven by Fe3+, whereas intracellular PDT resistance of the AIE PS was mitigated by sabutoclax. The design of the multifunctional hybrid nanospheres demonstrates a prospective nanoplatform for image-guided enhanced PDT of tumors.
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Affiliation(s)
- Leilei Shi
- Department of Chemical and Biomolecular Engineering , National University of Singapore , 4 Engineering Drive 4 , Singapore 117585
| | - Fang Hu
- Department of Chemical and Biomolecular Engineering , National University of Singapore , 4 Engineering Drive 4 , Singapore 117585
| | - Yukun Duan
- Department of Chemical and Biomolecular Engineering , National University of Singapore , 4 Engineering Drive 4 , Singapore 117585
| | - Wenbo Wu
- Department of Chemical and Biomolecular Engineering , National University of Singapore , 4 Engineering Drive 4 , Singapore 117585
| | - Jinqiao Dong
- Department of Chemical and Biomolecular Engineering , National University of Singapore , 4 Engineering Drive 4 , Singapore 117585
| | - Xiangjun Meng
- Department of Gastroenterology, Shanghai Ninth People's Hospital , Shanghai Jiao Tong University School of Medicine , 639 Zhizaoju Road , Shanghai 200011 , China
| | - Xinyuan Zhu
- School of Chemistry and Chemical Engineering , Shanghai Jiao Tong University , 800 Dongchuan Road , Shanghai 200240 , China
| | - Bin Liu
- Department of Chemical and Biomolecular Engineering , National University of Singapore , 4 Engineering Drive 4 , Singapore 117585
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12
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Bogoeva V, Petrova L, Bouckaert J, Yordanova A, Ivanov I, Vanderesse R, Frochot C. Dual function of lectins — new perspectives in targeted photodynamic therapy. J PORPHYR PHTHALOCYA 2020. [DOI: 10.1142/s1088424619300209] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Porphyrins and phthalocyanines are photosensitizers (PS) that are used in clinical imaging, detection of cancer cells and are particularly applied in photodynamic therapy (PDT). Many scientists have been focused on the design of different porphyrin compounds. However, similar to other anti-cancer agents, they cannot selectively recognize tumor tissues. Scientists are seeking new methods to overcome this problem and to find appropriate targeted delivery strategies. Plant lectins are especially suitable molecules for such targeting as they preferentially recognize specific antigens on the glycosylated cancer cells. This review will give more detailed information about the dual function of lectins and their interactions with PSs, which is a new perspective in targeted PDT. The implications and potential applications of such studies will also be discussed.
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Affiliation(s)
- Vanya Bogoeva
- Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences, “Acad. G. Bonchev”, Str. Bl. 21, 1113, Sofia, Bulgaria
| | - Lidiya Petrova
- Medical University of Pleven, Department of Anatomy, Histology, Cytology and Biology, 1, “Sv. Kliment Ohridski Str.”, 5800 Pleven, Bulgaria
| | - Julie Bouckaert
- Unité de Glycobiologie Structurale et Fonctionelle (UGSF), UMR 8576 of the University of Lille and CNRS, 50 Av. de Halley, 59658 Villeneuve d’Ascq, France
| | - Anna Yordanova
- Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences, “Acad. G. Bonchev”, Str. Bl. 21, 1113, Sofia, Bulgaria
| | - Ivan Ivanov
- Institute of Catalysis, Bulgarian Academy of Sciences, “Acad. G. Bonchev” Str., 1113, Sofia, Bulgaria
| | - Régis Vanderesse
- LCPM UMR 7375 CNRS-University of Lorraine, 1 rue Grandville, BP20451 54001 Nancy CEDEX, France
| | - Céline Frochot
- LRGP UMR 7274 CNRS-University of Lorraine, 1 rue Grandville, BP20451 54001 Nancy CEDEX, France
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Huang L, Lin H, Chen Q, Yu L, Bai D. MPPa-PDT suppresses breast tumor migration/invasion by inhibiting Akt-NF-κB-dependent MMP-9 expression via ROS. BMC Cancer 2019; 19:1159. [PMID: 31783821 PMCID: PMC6884812 DOI: 10.1186/s12885-019-6374-x] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 11/18/2019] [Indexed: 12/17/2022] Open
Abstract
Background Breast cancer is one of the most commonly diagnosed cancers in women, with high morbidity and mortality. Tumor metastasis is implicated in most breast cancer deaths; thus, inhibiting metastasis may provide a therapeutic direction for breast cancer. In the present study, pyropheophorbide-α methyl ester-mediated photodynamic therapy (MPPa-PDT) was used to inhibit metastasis in MCF-7 breast cancer cells. Methods Uptake of MPPa was detected by fluorescence microscopy. Cell viability was evaluated by the Cell Counting Kit-8 (CCK-8). ROS generation was detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA). The migration of cells was assessed by wound healing assay, and invasion ability was assessed by Matrigel invasion assay. Levels of MMP2 and MMP9 were measured by PCR. Akt, phospho-Akt (Ser473), phospho-NF-κB p65 (Ser536) and NF-κB p65 were measured by western blotting. The F-actin cytoskeleton was observed by immunofluorescence. Lung tissue was visualized by hematoxylin and eosin staining. Results Following MPPa-PDT, migration and invasion were decreased in the MCF-7 cells. MPPa-PDT downregulated the expression of MMP2 and MMP9, which are responsible for the initiation of metastasis. MPPa-PDT reduced the phosphorylation of Akt and NF-κB. MPPa-PDT also reduced the expression of F-actin in cytoskeleton in MCF-7 cells. These effects were blocked by the reactive oxygen species scavenger NAC or the Akt activator SC79, while the PI3K inhibitor LY294002 or the Akt inhibitor triciribine enhanced these effects. Moreover, MPPa-PDT inhibited tumor metastasis and destroyed F-actin in vivo. Conclusion Taken together, these results demonstrate that MPPa-PDT inhibits the metastasis of MCF-7 cells both in vitro and in vivo and may be involved in the Akt/NF-κB-dependent MMP-9 signaling pathway. Thus, MPPa-PDT may be a promising treatment to inhibit metastasis.
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Affiliation(s)
- Liyi Huang
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China
| | - Haidan Lin
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China
| | - Qing Chen
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China
| | - Lehua Yu
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People's Republic of China
| | - Dingqun Bai
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
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Jing Y, Lian-Nan L, Xiao-Bo Z, Yue W, Bing B, Guo-Cai Z, Chuan-Shan Z. Sodium pheophorbide a has photoactivated fungicidal activity against Pestalotiopsis neglecta. PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY 2019; 158:25-31. [PMID: 31378357 DOI: 10.1016/j.pestbp.2019.04.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 04/07/2019] [Accepted: 04/09/2019] [Indexed: 06/10/2023]
Abstract
Sodium pheophorbide a (SPA) is a natural photosensitizer. To explore its antifungal activity and mechanism, we studied its inhibitory effects on spore germination and mycelial growth of Pestalotiopsis neglecta. We used sorbitol, 2-thiobarbituric acid (TBA) and electron microscopy to determine its effects on cell wall integrity, cell membrane lipid peroxidation and mycelial morphology. Finally, the effects of SPA on enzyme activity in mycelia were determined. The results showed that SPA effectively inhibited spore germination and mycelial growth of P. neglecta under light conditions (4000 lx, 24 h). Scanning electron microscopy (SEM) revealed that SPA treatment resulted in a roughened, twisted and knotted mycelial surface and abnormal mycelial growth. SPA influenced cell wall integrity, and the content of MDA, a cell membrane lipid peroxidation product was significantly increased (P < 0.05). SPA also significantly inhibited SOD, POD and PG activity, but enhanced PPO activity (P < 0.05). In conclusion, SPA may have potential to become a biological pesticide.
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Affiliation(s)
- Yang Jing
- Heilongjiang Province Key Laboratory of Forest Protection, School of Forest, Northeast Forestry University, Hexing Road 26, Xiangfang District, Harbin 150040, PR China
| | - Lin Lian-Nan
- Heilongjiang Province Key Laboratory of Forest Protection, School of Forest, Northeast Forestry University, Hexing Road 26, Xiangfang District, Harbin 150040, PR China
| | - Zhang Xiao-Bo
- Heilongjiang Province Key Laboratory of Forest Protection, School of Forest, Northeast Forestry University, Hexing Road 26, Xiangfang District, Harbin 150040, PR China
| | - Wu Yue
- Heilongjiang Province Key Laboratory of Forest Protection, School of Forest, Northeast Forestry University, Hexing Road 26, Xiangfang District, Harbin 150040, PR China
| | - Bi Bing
- Heilongjiang Province Key Laboratory of Forest Protection, School of Forest, Northeast Forestry University, Hexing Road 26, Xiangfang District, Harbin 150040, PR China
| | - Zhang Guo-Cai
- Heilongjiang Province Key Laboratory of Forest Protection, School of Forest, Northeast Forestry University, Hexing Road 26, Xiangfang District, Harbin 150040, PR China.
| | - Zou Chuan-Shan
- Heilongjiang Province Key Laboratory of Forest Protection, School of Forest, Northeast Forestry University, Hexing Road 26, Xiangfang District, Harbin 150040, PR China
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Zhu T, Shi L, Yu C, Dong Y, Qiu F, Shen L, Qian Q, Zhou G, Zhu X. Ferroptosis Promotes Photodynamic Therapy: Supramolecular Photosensitizer-Inducer Nanodrug for Enhanced Cancer Treatment. Am J Cancer Res 2019; 9:3293-3307. [PMID: 31244955 PMCID: PMC6567978 DOI: 10.7150/thno.32867] [Citation(s) in RCA: 180] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 03/22/2019] [Indexed: 12/22/2022] Open
Abstract
The noninvasive nature of photodynamic therapy (PDT) enables the preservation of organ function in cancer patients. However, PDT is impeded by hypoxia in the tumor microenvironment (TME) caused by high intracellular oxygen (O2) consumption and distorted tumor blood vessels. Therefore, increasing oxygen generation in the TME would be a promising methodology for enhancing PDT. Herein, we proposed a concept of ferroptosis-promoted PDT based on the biochemical characteristics of cellular ferroptosis, which improved the PDT efficacy significantly by producing reactive oxygen species (ROS) and supplying O2 sustainably through the Fenton reaction. In contrast to traditional strategies that increase O2 based on decomposition of limited concentration of hydrogen peroxide (H2O2), our methodology could maintain the concentration of H2O2 and O2 through the Fenton reaction. Methods: For its association with sensitivity to ferroptosis, solute carrier family 7 member 11 (SLC7A11) expression was characterized by bioinformatics analysis and immunohistochemistry of oral tongue squamous cell carcinoma (OTSCC) specimens. Afterwards, the photosensitizer chlorin e6 (Ce6) and the ferroptosis inducer erastin were self-assembled into a novel supramolecular Ce6-erastin nanodrug through hydrogen bonding and π-π stacking. Then, the obtained Ce6-erastin was extensively characterized and its anti-tumor efficacy towards OTSCC was evaluated both in vitro and in vivo. Results: SLC7A11 expression is found to be upregulated in OTSCC, which is a potential target for ferroptosis-mediated OTSCC treatment. Ce6-erastin nanoparticles exhibited low cytotoxicity to normal tissues. More significantly, The over-accumulated intracellular ROS, increased O2 concentration and inhibited SLC7A11 expression lead to enhanced toxicity to CAL-27 cells and satisfactory antitumor effects to xenograft tumour mouse model upon irradiation. Conclusion: Our ferroptosis promoted PDT approach markedly enhances anticancer actions by relieving hypoxia and promoting ROS production, thereby our work provides a new approach for overcoming hypoxia-associated resistance of PDT in cancer treatment.
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16
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Yu W, Ye M, Zhu J, Wang Y, Liang C, Tang J, Tao H, Shen Y. Zinc phthalocyanine encapsulated in polymer micelles as a potent photosensitizer for the photodynamic therapy of osteosarcoma. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2018; 14:1099-1110. [PMID: 29462663 DOI: 10.1016/j.nano.2018.02.005] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/04/2017] [Revised: 01/17/2018] [Accepted: 02/08/2018] [Indexed: 12/11/2022]
Abstract
Zinc phthalocyanine (ZnPc) is a highly potent second-generation photosensitizer for cancer photodynamic therapy (PDT) with attractive photo-physical and photo-chemical properties. However, poor solubility and strong trend of crystallization prevent it from loading in most of drug delivery systems and hamper its further application. Herein, to overcome this problem, an amphiphilic block copolymer poly(ethylene glycol)-poly[2-(methylacryloyl)ethylnicotinate] (PEG-PMAN) with aromatic nicotinate is used to load ZnPc for their π-π interactions. The formed PEG-PMAN/ZnPc nanoparticle (PPZ) dramatically increases reactive oxygen species production in osteosarcoma cells after light irradiation, causes mitochondrial injury and promotes cell cycle arrest at G2/M, leading to a 100-fold cytotoxicity improvement comparing with free ZnPc. The excellent therapeutic effectiveness and safety of PPZ are also proved by in vivo experiments operating on osteosarcoma model. The finding above indicates that PPZ has promising clinical applications as a next-generation photosensitizer in PDT of osteosarcoma.
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Affiliation(s)
- Wei Yu
- Department of Orthopedics, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou, China
| | - Mingzhou Ye
- Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China
| | - Jian Zhu
- Department of Orthopedics, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou, China
| | - Yitian Wang
- Department of Orthopedics, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou, China
| | - Chengzhen Liang
- Department of Orthopedics, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou, China
| | - Jianbin Tang
- Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.
| | - Huimin Tao
- Department of Orthopedics, the 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China; Orthopedics Research Institute of Zhejiang University, Hangzhou, China.
| | - Youqing Shen
- Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Center for Bionanoengineering, and College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China
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Fakayode OJ, Tsolekile N, Songca SP, Oluwafemi OS. Applications of functionalized nanomaterials in photodynamic therapy. Biophys Rev 2018; 10:49-67. [PMID: 29294258 PMCID: PMC5803176 DOI: 10.1007/s12551-017-0383-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2017] [Accepted: 12/13/2017] [Indexed: 11/25/2022] Open
Abstract
Specially designed functionalized nanomaterials such as superparamagnetic iron oxide, gold, quantum dots and up- and down-conversion lanthanide series nanoparticles have consistently and completely revolutionized the biomedical environment over the past few years due to their specially inferring properties, such as specific drug delivery, plasmonic effect, optical and imaging properties, therapeutic thermal energy productionand excellent irresistible cellular penetration. These properties have been used to improve many existing disease treatment modalities and have led to the development of better therapeutic approaches for the advancement of the treatment of critical human diseases, such as cancers and related malaise. In photodynamic therapy, for example, where the delivery of therapeutic agents should ideally avoid toxicity on nearby healthy cells, superparamagnetic iron oxide nanoparticles have been shown to be capable of making photodynamic therapy (PDT) prodrugs and their associative targeting moieties tumor-specific via their unique response to an external magnetic fields. In this review, the nanomaterials commonly employed for the enhancement of photodynamic therapy are discussed. The review further describes the various methods of synthesis and characterization of these nanomaterials and highlights challenges for improving the efficacy of PDT in the future.
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Affiliation(s)
- Olayemi J Fakayode
- Department of Applied Chemistry, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa
- Centre for Nanomaterials Science Research, University of Johannesburg, Johannesburg, South Africa
| | - Ncediwe Tsolekile
- Department of Applied Chemistry, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa
- Centre for Nanomaterials Science Research, University of Johannesburg, Johannesburg, South Africa
| | - Sandile P Songca
- Department of Chemistry, University of Zululand, PB X1001, Kwadlangezwa, 3886, South Africa
| | - Oluwatobi S Oluwafemi
- Department of Applied Chemistry, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg, 2028, South Africa.
- Centre for Nanomaterials Science Research, University of Johannesburg, Johannesburg, South Africa.
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Doustvandi MA, Mohammadnejad F, Mansoori B, Mohammadi A, Navaeipour F, Baradaran B, Tajalli H. The interaction between the light source dose and caspase-dependent and -independent apoptosis in human SK-MEL-3 skin cancer cells following photodynamic therapy with zinc phthalocyanine: A comparative study. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY 2017; 176:62-68. [PMID: 28964887 DOI: 10.1016/j.jphotobiol.2017.09.020] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Revised: 09/03/2017] [Accepted: 09/21/2017] [Indexed: 12/12/2022]
Abstract
The aim of this study is to determine the behavior of relative expression of Bcl-2, caspase-8, caspase-9, and caspase-3 genes of/in SK-MEL-3 cancer cells and explore molecular mechanisms responsible for the apoptosis response during an in vitro photodynamic therapy (PDT) with Zinc Phthalocyanine (ZnPc) using different doses of the light source. In this study, firstly the cytotoxic effects of ZnPc-PDT on SK-MEL-3 cells were evaluated. By irradiating the laser, ZnPc induced a significant amount of apoptosis on SK-MEL-3 cells in three IC50s including 0.064±0.01, 0.043±0.01, and 0.036±0.01μg/mL at the doses of 8, 16, and 24J/cm2, respectively. Moreover, flow cytometry and QRT-PCR experiments were done. The high percentage of apoptotic cells was seen in the early apoptosis stage. The expression of Bcl-2 and caspase-8 genes at all doses of laser experienced an obvious reduction in comparison to the control group. On the other hand, although the expression of caspase-9 and caspase-3 genes remains almost constant at 8J/cm2, but they faced an increment at 16 and 24J/cm2 doses. These data reveal caspase-dependent apoptosis in high and caspase-independent apoptosis in low doses of laser. Based on the results of present work, it can be suggested that the dose of the light source is a key factor in induction of caspase-dependent and caspase-independent apoptosis pathways following PDT.
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Affiliation(s)
| | | | - Behzad Mansoori
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Mohammadi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Behzad Baradaran
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Habib Tajalli
- Research Institute for Applied Physics and Astronomy, University of Tabriz, Tabriz, Iran.
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Photodynamic process induced by chloro-aluminum phthalocyanine nanoemulsion in glioblastoma. Photodiagnosis Photodyn Ther 2017; 19:221-228. [DOI: 10.1016/j.pdpdt.2017.05.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 04/21/2017] [Accepted: 05/05/2017] [Indexed: 01/25/2023]
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Zhang X, Cai L, He J, Li X, Li L, Chen X, Lan P. Influence and mechanism of 5-aminolevulinic acid-photodynamic therapy on the metastasis of esophageal carcinoma. Photodiagnosis Photodyn Ther 2017; 20:78-85. [PMID: 28811223 DOI: 10.1016/j.pdpdt.2017.08.004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2017] [Revised: 07/19/2017] [Accepted: 08/08/2017] [Indexed: 11/29/2022]
Abstract
BACKGROUD Photodynamic therapy (PDT) for the treatment of esophageal cancer was more and more popularly used since it was approved for the treatment of advanced esophageal cancer in 1996. It has been reported to influence the tumor growth and metastasis via a variety of signaling pathways, but its mechanism remains to be further studied. This research studied the effects of ALA-PDT on esophageal carcinoma in vitro and in vivo, discovering its molecular regulating mechanism and the way to enhence the PDT effect. METHODS Eca-109 cells were incubated with a medium containing EGFR tyrphostin AG1478 or PI3K inhibitor LY294002, then with ALA, and the cells were irradiated with the laser 6h later. The cell viability was measured with MTT assay, and the migration ability was detected by transwell experiments 24h post-ALA-PDT. The gene and protein expression on EGFR/PI3K/AKT signaling pathway was analyzed by realtime PCR and Western blotting respectively. Then, RFP-Eca-109 burdened nude mice model was constructed, and were treated with ALA-PDT when the tumor volume reached 150-350mm3. The gene and protein expression were analyzed 24h and 50days post-ALA-PDT. RESULTS Our study showed that ALA-PDT respectively combined with AG1478, LY294002 could synergistically reduce the growth and migration ability of the Eca-109 cells in vitro and significantly down-regulate the protein expression of EGFR/PI3K and PI3K/AKT, meanwhile, significantly down-regulate the gene expression of EGFR when combining with AG1478. Forthermore, ALA-PDT could significantly decrease the tumor growth and metastasis and down-regulate the gene expression of EGFR and the protein expression of EGFR and PI3K in the tumor of mice. CONCLUSION This study revealed a molecular mechanism of ALA-PDT and developed a new modality application of therapy, by combining ALA-PDT with small molecular inhibitors, for better effect in the clinical practice of esophageal carcinoma.
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Affiliation(s)
- Xiaona Zhang
- The sixth affiliated hospital of SUN YAT-SEN University, Guangzhou, China
| | - Longmei Cai
- Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jingcai He
- Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, China
| | - Xiaoyan Li
- The sixth affiliated hospital of SUN YAT-SEN University, Guangzhou, China
| | - Libo Li
- Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, China.
| | - Xiaohua Chen
- Department of Oncology, Panyu Central Hospital, Cancer Institute of Panyu, Guangzhou, China.
| | - Ping Lan
- The sixth affiliated hospital of SUN YAT-SEN University, Guangzhou, China.
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Brito LDC, Berenger ALR, Figueiredo MR. An overview of anticancer activity of Garcinia and Hypericum. Food Chem Toxicol 2017; 109:847-862. [PMID: 28363851 DOI: 10.1016/j.fct.2017.03.053] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2017] [Revised: 03/12/2017] [Accepted: 03/14/2017] [Indexed: 01/01/2023]
Abstract
Cancer is one of the leading causes of death worldwide (approximately 8.2 million cases/year) and, over the next two decades, a 70% increase in new cancer cases is expected. Through analysis of the available drugs between the years of 1930 and 2014, it was found that 48% were either natural products or their derivatives. This proportion increased to 66% when semi-synthetic products were included. The family Clusiaceae Juss. (Malpighiales) includes approximately 1000 species distributed throughout all tropical and temperate regions. The phytochemical profile of this family includes many chemicals with interesting pharmacological activities, including anticancer activities. This study includes an overview of the in vitro and in vivo anticancer activity of secondary metabolites from Garcinia and Hypericum and the mechanisms involved in this activity. Hypericum no longer belong to Clusiaceae family, but was considered in the past by taxonomists, due to similarities with this family. Research in the area has shown that several compounds belonging to different chemical classes exhibit activity in several tumor cell lines in different experimental models. This review shows the significant antineoplasic activity of these compounds, in particular of these two genera and validates the importance of natural products in the search for anticancer drugs.
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Affiliation(s)
- Lavínia de C Brito
- Central Analítica Fernanda Coutinho, Instituto de Química, UERJ, Rio de Janeiro, RJ, Brazil; Laboratório de Produtos Naturais 3 (PN3), FIOCRUZ, Rio de Janeiro, RJ, Brazil.
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Abramczyk H, Brozek-Pluska B, Surmacki J, Tondusson M, Freysz E. Photostability of biological systems—Femtosecond dynamics of zinc tetrasulfonated phthalocyanine at cancerous and noncancerous human Breast tissues. J Photochem Photobiol A Chem 2017. [DOI: 10.1016/j.jphotochem.2016.08.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Grigalavicius M, Juraleviciute M, Kwitniewski M, Juzeniene A. The influence of photodynamic therapy with 5-aminolevulinic acid on senescent skin cancer cells. Photodiagnosis Photodyn Ther 2016; 17:29-34. [PMID: 27777143 DOI: 10.1016/j.pdpdt.2016.10.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 10/13/2016] [Accepted: 10/20/2016] [Indexed: 11/28/2022]
Abstract
BACKGROUND Senescent cells, which are resistant to apoptosis, accumulate with age and after ultraviolet (UV) radiation, chemotherapy and radiation therapy. Preventing or eliminating senescent cells may be crucial for protection against skin cancer development and improving tumour treatment. The aim of the present study was to investigate the potential of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) to induce senescence in skin cancer cells and to eliminate senescent cells induced by chemotherapy (bleomycin) or UVA (315-400nm) exposure. METHODS WM115 and A431 cells were incubated with 1mM ALA for 2 and 4h, respectively, before exposure to blue light (10mW/cm2, 0-80s, 0-0.8J/cm2). WM115 cells were treated once with 106J/cm2 (58.4mW/cm2, 30.25min) UVA 6days before ALA-PDT or with 0.24IU/ml bleomycin for 7days to induce senescence before ALA-PDT. Cell viability was monitored by the MTT colorimetric assay. Senescent cells were detected using senescence-associated-beta-galactosidase (SA-β-Gal) staining and morphological changes (enlarged, flat cells). RESULTS ALA-PDT caused a light dose dependent increase in senescence. ALA-PDT induced senescence very effectively only in WM115 cells but not in A431 cells, while similar cytotoxic effects were observed in both cell lines. After ALA-PDT with 0.4J/cm2 around 70% of survived WM115 cells were senescent, while only around 5% of A431 cells were senescent after ALA-PDT with 0.8J/cm2. CONCLUSION ALA-PDT can induce premature senescence and kill senescent cells induced by ALA-PDT itself, UVA and chemotherapy (bleomycin). Light doses must be properly chosen to photoinactivate ALA-PDT-induced senescent cells.
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Affiliation(s)
- Mantas Grigalavicius
- Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway
| | - Marina Juraleviciute
- Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway
| | - Mateusz Kwitniewski
- Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 7 Gronostajowa Street, 30-387 Krakow, Poland
| | - A Juzeniene
- Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway.
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Malina L, Tomankova KB, Malohlava J, Jiravova J, Manisova B, Zapletalova J, Kolarova H. The in vitro cytotoxicity of metal-complexes of porphyrin sensitizer intended for photodynamic therapy. Toxicol In Vitro 2016; 34:246-256. [DOI: 10.1016/j.tiv.2016.04.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 04/15/2016] [Accepted: 04/18/2016] [Indexed: 10/21/2022]
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Luiza Andreazza N, Vevert-Bizet C, Bourg-Heckly G, Sureau F, José Salvador M, Bonneau S. Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins. Int J Pharm 2016; 510:240-9. [DOI: 10.1016/j.ijpharm.2016.06.009] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 05/30/2016] [Accepted: 06/05/2016] [Indexed: 01/30/2023]
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Abstract
Cationic porphyrins (Prs) and phthalocyanines (Pcs) are strong photosensitizers that have drawn much attention for their potential in photodynamic therapy. These compounds have the interesting property of binding to nucleic acids, in particular G-rich quadruplex-forming sequences in DNA and RNA. In this review, we highlight their potential as anticancer drugs.
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Acedo P, Zawacka-Pankau J. p53 family members - important messengers in cell death signaling in photodynamic therapy of cancer? Photochem Photobiol Sci 2015. [PMID: 26202022 DOI: 10.1039/c5pp00251f] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
TP53 is one of the genes most frequently inactivated in cancers. Mutations in TP53 gene are linked to worse prognosis and shorter overall survival of cancer patients. TP53 encodes a critical tumor suppressor, which dictates cell fate decisions upon stress stimuli. As a sensor of cellular stress, p53 is a relevant messenger of cell death signaling in ROS-driven photodynamic therapy (PDT) of cancer. The significant role of p53 in response to PDT has been reported for several clinically approved photosensitizers. Multiple reports described that wild-type p53 contributes to cell killing upon photodynamic therapy with clinically approved photosensitizers but the mechanism is still not fully understood. This work outlines the diverse functions of p53 family members in cancer cells' susceptibility and resistance to PDT. In summary p53 and p53 family members are emerging as important mediators of cell death signaling in photodynamic therapy of cancer, however the mechanism of cell death provoked during PDT might differ depending on the tissue type and the photosensitizer applied.
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Affiliation(s)
- Pilar Acedo
- Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Nobels väg 16, 171 77 Stockholm, Sweden.
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Benković ET, Kreft S. Fagopyrins and Protofagopyrins: Detection, Analysis, and Potential Phototoxicity in Buckwheat. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2015; 63:5715-5724. [PMID: 26024291 DOI: 10.1021/acs.jafc.5b01163] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Buckwheat contains many healthy nutrients, and its consumption is therefore increasing. Buckwheat also contains fluorescent phototoxic fagopyrins. A systematic review of fagopyrins and the phototoxicity of buckwheat found that reliable quantitative data on fagopyrin toxicity are not yet available. Generally, buckwheat seeds, flour, and teas are safe in normal amounts. Diets extensively composed of buckwheat sprouts, herbs, and particularly flowers or of fagopyrin-rich buckwheat extracts may cause fagopyrism. A reference standard is needed, as it would enable the accurate evaluation of fagopyrin content in buckwheat products and would allow proper testing of their as yet unknown physical, chemical, and biological characteristics.
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Affiliation(s)
- Eva Tavčar Benković
- Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia
| | - Samo Kreft
- Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia
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29
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Yousaf A, Hamid SA, Bunnori NM, Ishola AA. Applications of calixarenes in cancer chemotherapy: facts and perspectives. DRUG DESIGN DEVELOPMENT AND THERAPY 2015; 9:2831-8. [PMID: 26082613 PMCID: PMC4459628 DOI: 10.2147/dddt.s83213] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Research on the therapeutic applications of calixarene derivatives is an emerging area of interest. The anticancer activity of various functionalized calixarenes has been reported by several research groups. Due to their superior geometric shape, calixarenes can accommodate drug molecules by forming inclusion complexes. Controlled release of anticancer drugs by calixarenes might help in targeted chemotherapy. This review summarizes the anticancer potential of the calixarenes and their drug loading properties. The potential use of calixarenes in chemoradiotherapy is also highlighted in brief.
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Affiliation(s)
- Ali Yousaf
- Kulliyyah of Science, International Islamic University Malaysia, Bandar Indera Mahkota, Malaysia
| | - Shafida Abd Hamid
- Kulliyyah of Science, International Islamic University Malaysia, Bandar Indera Mahkota, Malaysia
| | - Noraslinda M Bunnori
- Kulliyyah of Science, International Islamic University Malaysia, Bandar Indera Mahkota, Malaysia
| | - A A Ishola
- Kulliyyah of Medicine, International Islamic University Malaysia, Bandar Indera Mahkota, Malaysia
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Wang YT, Qin YJ, Yang N, Zhang YL, Liu CH, Zhu HL. Synthesis, biological evaluation, and molecular docking studies of novel 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole derivatives as potential tubulin polymerization inhibitors. Eur J Med Chem 2015; 99:125-37. [PMID: 26070164 DOI: 10.1016/j.ejmech.2015.05.021] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Revised: 05/11/2015] [Accepted: 05/13/2015] [Indexed: 11/19/2022]
Abstract
A series of 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole derivatives were designed, synthesized and evaluated as potential tubulin polymerization inhibitors and for the cytotoxicity against anthropic cancer cell lines. Among the novel compounds, compound 11f was demonstrated the most potent tubulin polymerization inhibitory activity (IC50 = 1.5 μM) and antiproliferative activity against A549, HepG2 and MCF-7 (GI50 = 2.4, 3.8 and 5.1 μM, respectively), which was compared with the positive control colchicine and CA-4. We also evaluated that compound 11f could effectively induce apoptosis of A549 associated with G2/M phase cell cycle arrest. Docking simulation and 3D-QSAR model in these studies provided more information that could be applied to design new molecules with more potent tubulin inhibitory activity.
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Affiliation(s)
- Yan-Ting Wang
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China
| | - Ya-Juan Qin
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China
| | - Na Yang
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China
| | - Ya-Liang Zhang
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China
| | - Chang-Hong Liu
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China
| | - Hai-Liang Zhu
- State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
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31
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Ali S, Khurshid A, Maqsood M, Rafi M, Khan JA, Zaidi S, Mohammad S, Ikram M. Study of low doses cisplatin synergistic effect on photodynamic outcome of aluminum phythalocyanine on soft tissue sarcoma (RD) cell line. Photodiagnosis Photodyn Ther 2015; 12:146-9. [DOI: 10.1016/j.pdpdt.2014.12.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 12/23/2014] [Accepted: 12/26/2014] [Indexed: 11/26/2022]
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32
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Berstad MB, Cheung LH, Berg K, Peng Q, Fremstedal ASV, Patzke S, Rosenblum MG, Weyergang A. Design of an EGFR-targeting toxin for photochemical delivery: in vitro and in vivo selectivity and efficacy. Oncogene 2015; 34:5582-92. [DOI: 10.1038/onc.2015.15] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2014] [Revised: 12/16/2014] [Accepted: 01/02/2015] [Indexed: 12/24/2022]
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Selbo PK, Bostad M, Olsen CE, Edwards VT, Høgset A, Weyergang A, Berg K. Photochemical internalisation, a minimally invasive strategy for light-controlled endosomal escape of cancer stem cell-targeting therapeutics. Photochem Photobiol Sci 2015; 14:1433-50. [DOI: 10.1039/c5pp00027k] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Despite progress in radio-, chemo- and photodynamic-therapy (PDT) of cancer, treatment resistance still remains a major problem for patients with aggressive tumours.
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Affiliation(s)
- Pål Kristian Selbo
- Department of Radiation Biology
- Institute for Cancer Research
- The Norwegian Radium Hospital
- Oslo University Hospital
- Montebello
| | - Monica Bostad
- Department of Radiation Biology
- Institute for Cancer Research
- The Norwegian Radium Hospital
- Oslo University Hospital
- Montebello
| | - Cathrine Elisabeth Olsen
- Department of Radiation Biology
- Institute for Cancer Research
- The Norwegian Radium Hospital
- Oslo University Hospital
- Montebello
| | - Victoria Tudor Edwards
- Department of Radiation Biology
- Institute for Cancer Research
- The Norwegian Radium Hospital
- Oslo University Hospital
- Montebello
| | - Anders Høgset
- Cancer Stem Cell Innovation Center (SFI-CAST)
- Institute for Cancer Research
- Norwegian Radium Hospital
- Oslo University Hospital
- Oslo
| | - Anette Weyergang
- Department of Radiation Biology
- Institute for Cancer Research
- The Norwegian Radium Hospital
- Oslo University Hospital
- Montebello
| | - Kristian Berg
- Department of Radiation Biology
- Institute for Cancer Research
- The Norwegian Radium Hospital
- Oslo University Hospital
- Montebello
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Piette J. Signalling pathway activation by photodynamic therapy: NF-κB at the crossroad between oncology and immunology. Photochem Photobiol Sci 2015; 14:1510-7. [DOI: 10.1039/c4pp00465e] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The response of tumors to photodynamic therapy (PDT) largely depend on signaling pathways among which the pathway leading to NF-κB activation is of high importance.
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Affiliation(s)
- Jacques Piette
- Laboratory of Virology & Immunology
- GIGA-Signal Transduction
- GIGA B34
- University of Liège
- B-4000 Liège
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35
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Soriano J, Villanueva A, Stockert JC, Cañete M. Regulated necrosis in HeLa cells induced by ZnPc photodynamic treatment: a new nuclear morphology. Int J Mol Sci 2014; 15:22772-85. [PMID: 25501332 PMCID: PMC4284736 DOI: 10.3390/ijms151222772] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 11/03/2014] [Accepted: 12/01/2014] [Indexed: 12/05/2022] Open
Abstract
Photodynamic therapy (PDT) is a cancer treatment modality based on the administration of a photosensitizer (PS), which accumulates preferentially in tumor cells. Subsequent irradiation of the neoplastic area triggers a cascade of photochemical reactions that leads to the formation of highly reactive oxygen species responsible for cell inactivation. Photodynamic treatments in vitro are performed with the PS, zinc-phthalocyanine (ZnPc). The PS is near the plasma membrane during uptake and internalization. Inactivation clearly occurs by a necrotic process, manifested by nuclear pyknosis, negative TUNEL and Annexin V assays and non-relocation of cytochrome c. In contrast, by increasing the incubation time, ZnPc is accumulated in the Golgi apparatus and produces cell inactivation with characteristics of apoptosis and necrosis: TUNEL positive, relocated cytochrome c and negative Annexin V assay. This type of death produces a still undescribed granulated nuclear morphology, which is different from that of necrosis or apoptosis. This morphology is inhibited by necrostatin-1, a specific inhibitor of regulated necrosis.
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Affiliation(s)
- Jorge Soriano
- Department of Biology, University Autonomous of Madrid, 28049 Madrid, Spain.
| | - Angeles Villanueva
- Department of Biology, University Autonomous of Madrid, 28049 Madrid, Spain.
| | | | - Magdalena Cañete
- Department of Biology, University Autonomous of Madrid, 28049 Madrid, Spain.
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Nagai Y, Aizawa S, Iriuchishima T, Goto B, Nagaoka M, Tokuhashi Y, Saito A. Phototoxic effect of na-pheophorbide a toward osteosarcoma cells in vitro using a laser diode. Photomed Laser Surg 2014; 32:481-9. [PMID: 25105597 DOI: 10.1089/pho.2014.3736] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
OBJECTIVE The purpose of this study was to investigate the effectiveness of photodynamic therapy (PDT) with Na-pheophorbide A in anticancer treatment, using osteosarcoma cells in vitro. BACKGROUND DATA It has been reported that PDT with chlorophyll derivatives inhibits the proliferation of various cancer cells. However, there have been no reports that have evaluated the effectiveness of PDT in suppressing osteosarcoma cells. MATERIALS AND METHODS Uptake of Na-pheophorbide A into Hu09 cells (osteosarcoma cells) was assayed using fluorescence microscopy following incubation of the cells with 28 μmol/L of Na-pheophorbide A. The viability of Hu09 cells after PDT treatment was assessed using trypan blue dye staining and MTS assays. PDT-induced apoptosis was determined by evaluation of the activity of selected members of the caspase family and by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of cells. RESULTS Na-pheophorbide A uptake by cells was rapid, being observed after 60 min of treatment, and Na-pheophorbide A persisted in cells for >24 h. PDT treatment decreased cell viability compared with the control group, indicating high cytocidal activity of PDT. This cytocidal effect was dependent upon drug concentration, light dose, and the number of irradiation times. An increase in the number of cells positive for TUNEL staining and increases in the activity of caspases-3, -8 and -9 were observed in the first 2 h after PDT treatment. CONCLUSIONS A cytotoxic effect of PDT with Na-pheophorbide A on an osteosarcoma cell line in vitro was shown. Caspase activity assays suggested that PDT with Na-pheophorbide A induced an apoptotic change in HuO9 cells, mainly via activation of mitochondrial caspase -9 and -3 pathways.
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Affiliation(s)
- Yu Nagai
- 1 Department of Orthopedic Surgery, Surugadai Nihon University Hospital , Tokyo, Japan
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37
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Lu YG, Wang YY, Yang YD, Zhang XC, Gao Y, Yang Y, Zhang JB, Li GL. Efficacy of topical ALA-PDT combined with excision in the treatment of skin malignant tumor. Photodiagnosis Photodyn Ther 2014; 11:122-6. [DOI: 10.1016/j.pdpdt.2014.02.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Revised: 12/29/2013] [Accepted: 02/13/2014] [Indexed: 10/25/2022]
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38
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Wei MF, Chen MW, Chen KC, Lou PJ, Lin SYF, Hung SC, Hsiao M, Yao CJ, Shieh MJ. Autophagy promotes resistance to photodynamic therapy-induced apoptosis selectively in colorectal cancer stem-like cells. Autophagy 2014; 10:1179-92. [PMID: 24905352 PMCID: PMC4203546 DOI: 10.4161/auto.28679] [Citation(s) in RCA: 160] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Recent studies have indicated that cancer stem-like cells (CSCs) exhibit a high resistance to current therapeutic strategies, including photodynamic therapy (PDT), leading to the recurrence and progression of colorectal cancer (CRC). In cancer, autophagy acts as both a tumor suppressor and a tumor promoter. However, the role of autophagy in the resistance of CSCs to PDT has not been reported. In this study, CSCs were isolated from colorectal cancer cells using PROM1/CD133 (prominin 1) expression, which is a surface marker commonly found on stem cells of various tissues. We demonstrated that PpIX-mediated PDT induced the formation of autophagosomes in PROM1/CD133+ cells, accompanied by the upregulation of autophagy-related proteins ATG3, ATG5, ATG7, and ATG12. The inhibition of PDT-induced autophagy by pharmacological inhibitors and silencing of the ATG5 gene substantially triggered apoptosis of PROM1/CD133+ cells and decreased the ability of colonosphere formation in vitro and tumorigenicity in vivo. In conclusion, our results revealed a protective role played by autophagy against PDT in CSCs and indicated that targeting autophagy could be used to elevate the PDT sensitivity of CSCs. These findings would aid in the development of novel therapeutic approaches for CSC treatment.
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Affiliation(s)
- Ming-Feng Wei
- Institute of Biomedical Engineering; National Taiwan University; Taipei, Taiwan
| | - Min-Wei Chen
- Department of Oncology; National Taiwan University Hospital; Taipei, Taiwan
| | - Ke-Cheng Chen
- Institute of Biomedical Engineering; National Taiwan University; Taipei, Taiwan; Department of Surgery; National Taiwan University Hospital; Taipei, Taiwan
| | - Pei-Jen Lou
- Department of Otolaryngology; National Taiwan University Hospital; Taipei, Taiwan
| | - Susan Yun-Fan Lin
- Institute of Biomedical Engineering; National Taiwan University; Taipei, Taiwan
| | - Shih-Chieh Hung
- Institute of Clinical Medicine; National Yang-Ming University; Taipei, Taiwan
| | - Michael Hsiao
- Genomics Research Center; Academia Sinica; Taipei, Taiwan
| | - Cheng-Jung Yao
- Gastroenterology; Taipei Medical University-Municipal Wan Fang Hospital; Taipei, Taiwan
| | - Ming-Jium Shieh
- Institute of Biomedical Engineering; National Taiwan University; Taipei, Taiwan; Department of Oncology; National Taiwan University Hospital; Taipei, Taiwan
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39
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Antonenko YN, Kotova EA, Omarova EO, Rokitskaya TI, Ol'shevskaya VA, Kalinin VN, Nikitina RG, Osipchuk JS, Kaplan MA, Ramonova AA, Moisenovich MM, Agapov II, Kirpichnikov MP. Photodynamic activity of the boronated chlorin e6 amide in artificial and cellular membranes. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2014; 1838:793-801. [DOI: 10.1016/j.bbamem.2013.11.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2013] [Revised: 11/15/2013] [Accepted: 11/18/2013] [Indexed: 12/18/2022]
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Bœuf G, Roullin GV, Moreau J, Van Gulick L, Zambrano Pineda N, Terryn C, Ploton D, Andry MC, Chuburu F, Dukic S, Molinari M, Lemercier G. Encapsulated Ruthenium(II) Complexes in Biocompatible Poly(d,l-lactide-co-glycolide) Nanoparticles for Application in Photodynamic Therapy. Chempluschem 2014; 79:171-180. [DOI: 10.1002/cplu.201300242] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2013] [Revised: 11/12/2013] [Indexed: 01/23/2023]
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41
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Malatesta M, Pellicciari C, Cisterna B, Costanzo M, Galimberti V, Biggiogera M, Zancanaro C. Tracing nanoparticles and photosensitizing molecules at transmission electron microscopy by diaminobenzidine photo-oxidation. Micron 2013; 59:44-51. [PMID: 24530364 DOI: 10.1016/j.micron.2013.12.007] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Revised: 12/12/2013] [Accepted: 12/12/2013] [Indexed: 11/29/2022]
Abstract
During the last three decades, diaminobenzidine photo-oxidation has been applied in a variety of studies to correlate light and electron microscopy. Actually, when a fluorophore is excited by light, it can induce the oxidation of diaminobenzidine into an electron-dense osmiophilic product, which precipitates in close proximity to the fluorophore, thereby allowing its ultrastructural detection. This method has very recently been developed for two innovative applications: tracking the fate of fluorescently labeled nanoparticles in single cells, and detecting the subcellular location of photo-active molecules suitable for photodynamic therapy. These studies established that the cytochemical procedures exploiting diaminobenzidine photo-oxidation represent a reliable tool for detecting, inside the cells, with high sensitivity fluorescing molecules. These procedures are trustworthy even if the fluorescing molecules are present in very low amounts, either inside membrane-bounded organelles, or at the surface of the plasma membrane, or free in the cytosol. In particular, diaminobenzidine photo-oxidation allowed elucidating the mechanisms responsible for nanoparticles internalization in neuronal cells and for their escape from lysosomal degradation. As for the photo-active molecules, their subcellular distribution at the ultrastructural level provided direct evidence for the lethal multiorganelle photo-damage occurring after cell photo-sensitization. In addition, DAB photo-oxidized samples are suitable for the ultrastructural detection of organelle-specific molecules by post-embedding gold immunolabeling.
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Affiliation(s)
- M Malatesta
- Department of Neurological and Movement Sciences (Anatomy and Histology Section), University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
| | - C Pellicciari
- Department of Biology and Biotechnology "Lazzaro Spallanzani" (Laboratory of Cell Biology and Neurobiology), University of Pavia, Via A. Ferrata, 9, 27100 Pavia, Italy.
| | - B Cisterna
- Department of Neurological and Movement Sciences (Anatomy and Histology Section), University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
| | - M Costanzo
- Department of Neurological and Movement Sciences (Anatomy and Histology Section), University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
| | - V Galimberti
- Department of Biology and Biotechnology "Lazzaro Spallanzani" (Laboratory of Cell Biology and Neurobiology), University of Pavia, Via A. Ferrata, 9, 27100 Pavia, Italy.
| | - M Biggiogera
- Department of Biology and Biotechnology "Lazzaro Spallanzani" (Laboratory of Cell Biology and Neurobiology), University of Pavia, Via A. Ferrata, 9, 27100 Pavia, Italy.
| | - C Zancanaro
- Department of Neurological and Movement Sciences (Anatomy and Histology Section), University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
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Woźniak M, Hotowy K, Czapińska E, Duś-Szachniewicz K, Szczuka I, Gamian E, Gamian A, Terlecki G, Ziółkowski P. Early induction of stress-associated Src activator/Homo sapiens chromosome 9 open reading frame 10 protein following photodynamic therapy. Photodiagnosis Photodyn Ther 2013; 11:27-33. [PMID: 24280438 DOI: 10.1016/j.pdpdt.2013.11.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 11/12/2013] [Accepted: 11/13/2013] [Indexed: 11/28/2022]
Abstract
BACKGROUND There are proteins, responsible for many basic cell functions (transmission of extracellular signals to cytoplasm or nucleus, cell growth, proliferation, migration, survival), which are activated and overexpressed in response to acute oxidative stress, especially tyrosine kinases. The oxidative stress-associated Src activator/Homo sapiens chromosome 9 open reading frame 10 protein (Ossa/C9orf10) protects cancer cells from oxidative stress-induced apoptosis by Src family kinases activation. METHODS In this study precursor of protoporphyrin IX, 5-aminolevulinic acid and its encapsulated form were used in treating MCF-7 human breast cancer cells. After light illumination, cells were collected at different time points and used for evaluation (immunocytochemistry, Western blot analysis) of expression of above proteins, c-Src and Ossa. RESULTS Our results showed that 5-aminolevulinic acid-mediated photodynamic therapy caused decrease of c-Src expression at 7h after irradiation. The strongest expression was observed at 24h after treatment. Encapsulated form of 5-aminolevulinic acid in terms of PDT caused similar changes of expression of c-Src protein. Furthermore, we observed strong Ossa expression at 7h after treatment in comparison to very low expression at time points 0, 18 and 24h. CONCLUSION We would like to emphasize that our results showed high expression of Ossa at early time interval after PDT, which was accompanied by a low expression of c-Src kinase, what could protect cancer cells from PDT through activation of c-Src in response to oxidative stress.
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Affiliation(s)
- Marta Woźniak
- Department of Pathology, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Katarzyna Hotowy
- Department of Medical Biochemistry, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Elżbieta Czapińska
- Department of Medical Biochemistry, Wrocław Medical University, 50-367 Wrocław, Poland
| | | | - Izabela Szczuka
- Department of Medical Biochemistry, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Elżbieta Gamian
- Department of Pathology, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Andrzej Gamian
- Department of Medical Biochemistry, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Grzegorz Terlecki
- Department of Medical Biochemistry, Wrocław Medical University, 50-367 Wrocław, Poland
| | - Piotr Ziółkowski
- Department of Pathology, Wrocław Medical University, 50-367 Wrocław, Poland.
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Kushibiki T, Hirasawa T, Okawa S, Ishihara M. Regulation of miRNA expression by low-level laser therapy (LLLT) and photodynamic therapy (PDT). Int J Mol Sci 2013; 14:13542-58. [PMID: 23807510 PMCID: PMC3742202 DOI: 10.3390/ijms140713542] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2013] [Revised: 06/19/2013] [Accepted: 06/20/2013] [Indexed: 12/13/2022] Open
Abstract
Applications of laser therapy, including low-level laser therapy (LLLT), phototherapy and photodynamic therapy (PDT), have been proven to be beneficial and relatively less invasive therapeutic modalities for numerous diseases and disease conditions. Using specific types of laser irradiation, specific cellular activities can be induced. Because multiple cellular signaling cascades are simultaneously activated in cells exposed to lasers, understanding the molecular responses within cells will aid in the development of laser therapies. In order to understand in detail the molecular mechanisms of LLLT and PDT-related responses, it will be useful to characterize the specific expression of miRNAs and proteins. Such analyses will provide an important source for new applications of laser therapy, as well as for the development of individualized treatments. Although several miRNAs should be up- or down-regulated upon stimulation by LLLT, phototherapy and PDT, very few published studies address the effect of laser therapy on miRNA expression. In this review, we focus on LLLT, phototherapy and PDT as representative laser therapies and discuss the effects of these therapies on miRNA expression.
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Affiliation(s)
- Toshihiro Kushibiki
- Department of Medical Engineering, National Defense Medical College 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
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44
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Kushibiki T, Hirasawa T, Okawa S, Ishihara M. Responses of Cancer Cells Induced by Photodynamic Therapy. JOURNAL OF HEALTHCARE ENGINEERING 2013; 4:87-108. [DOI: 10.1260/2040-2295.4.1.87] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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45
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Pellicciari C, Giagnacovo M, Cisterna B, Costanzo M, Croce AC, Bottiroli G, Malatesta M. Ultrastructural detection of photosensitizing molecules by fluorescence photoconversion of diaminobenzidine. Histochem Cell Biol 2012; 139:863-71. [DOI: 10.1007/s00418-012-1071-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/27/2012] [Indexed: 12/14/2022]
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46
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Baltazar LDM, Soares BM, Carneiro HCS, Avila TV, Gouveia LF, Souza DG, Ferreira MVL, Pinotti M, Santos DDA, Cisalpino PS. Photodynamic inhibition of Trichophyton rubrum: in vitro activity and the role of oxidative and nitrosative bursts in fungal death. J Antimicrob Chemother 2012; 68:354-61. [DOI: 10.1093/jac/dks414] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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Yoo JO, Ha KS. New insights into the mechanisms for photodynamic therapy-induced cancer cell death. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2012; 295:139-74. [PMID: 22449489 DOI: 10.1016/b978-0-12-394306-4.00010-1] [Citation(s) in RCA: 108] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Photodynamic therapy (PDT) is a promising therapeutic modality for cancer treatment; however, a more detailed understanding is needed to improve the clinical use of this therapy. PDT induces cancer cell death by apoptosis, necrosis, and autophagy, and these mechanisms can be concurrently occurred. PDT destroys cancer cells by inducing apoptosis through diverse signaling pathways coupled with Bcl-2 family members, caspases, and apopotosis-inducing factor. When the apoptotic pathway is unavailable, PDT can cause cancer cell death through induction of a necrotic or autophagic mechanism. Autophagy is occurred in a Bax-independent manner and can be stimulated in parallel with apoptosis. PDT directly destroys cancer cells by inducing either apoptotic or necrotic death. PDT also can induce autophagy as a death or a survival mechanism. These mechanisms are dependent on a variety of parameters including the nature of the photosensitizer, PDT dose, and cell genotype. Understanding the complex cross talk between these pathways may improve the effectiveness of PDT. Here, we discuss the interplay between these mechanisms based on recent evidence and suggest prospects with regard to advances in PDT.
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Affiliation(s)
- Je-Ok Yoo
- Department of Molecular and Cellular Biochemistry, Kangwon National University School of Medicine, Chuncheon, Kangwon-do, South Korea
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Rapozzi V, Umezawa K, Xodo LE. Role of NF-κB/Snail/RKIP loop in the response of tumor cells to photodynamic therapy. Lasers Surg Med 2012; 43:575-85. [PMID: 22057485 DOI: 10.1002/lsm.21095] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND OBJECTIVE Photodynamic therapy (PDT) is a therapeutic modality whose efficacy depends on several factors including type of photosensitizer, light fluence and cellular response. Cell recurrence is one of the problems still unsolved in PDT. In this work we found that in B78-H1 murine amelanotic melanoma cells there is a correlation between cell recurrence and the NF-κB/Snail/RKIP loop. MATERIALS AND METHODS Proliferation and migration of surviving cells were analyzed by MTT and wound-scratch assays. The levels of ROS/NO in B78-H1 melanoma cells treated with pheophorbide a (Pba) and light (Pba/PDT) were measured by FACS, while expression of NF-κB, Snail and RKIP were determined by Western blots. The mechanism of cell death was investigated by caspase and microscopy assays. RESULTS Our data show that after a low-dose Pba/PDT treatment, B78-H1 cells are able to recover. This correlates with a low level of NO production, which blocks apoptosis via NF-κB pathway. Western blot analyses showed that a low-dose Pba/PDT increases the expression of NF-κB and anti-apoptotic Snail, but reduces the expression of pro-apoptotic RKIP. The role played by NF-κB in the modulation of Snail and RKIP was investigated using DHMEQ: a NF-κB inhibitor which behaves as NO donor. DHMEQ caused a decrease of Snail and an increase of RKIP expression. When B78-H1 cells were treated with a low dose Pba/PDT and DHMEQ, the NO level strongly increased, with the result that Snail was down-regulated and RKIP was upregulated, as observed with a high-dose Pba/PDT. CONCLUSION One major problem in PDT is the cellular rescue occurring in tissue regions receiving a low-dose PDT. To minimize this problem and sensitize cancer cells to PDT we propose a combined treatment in which the photosensitizer is delivered with a donor of NO acting on the NF-κB/Snail/RKIP loop.
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Affiliation(s)
- Valentina Rapozzi
- Department of Medical and Biological Science, School of Medicine, University of Udine, Udine 33100, Italy.
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Master AM, Livingston M, Oleinick NL, Sen Gupta A. Optimization of a nanomedicine-based silicon phthalocyanine 4 photodynamic therapy (Pc 4-PDT) strategy for targeted treatment of EGFR-overexpressing cancers. Mol Pharm 2012; 9:2331-8. [PMID: 22775587 DOI: 10.1021/mp300256e] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The current clinical mainstays for cancer treatment, namely, surgical resection, chemotherapy, and radiotherapy, can cause significant trauma, systemic toxicity, and functional/cosmetic debilitation of tissue, especially if repetitive treatment becomes necessary due to tumor recurrence. Hence there is significant clinical interest in alternate treatment strategies like photodynamic therapy (PDT) which can effectively and selectively eradicate tumors and can be safely repeated if needed. We have previously demonstrated that the second-generation photosensitizer Pc 4 (silicon phthalocyanine 4) can be formulated within polymeric micelles, and these micelles can be specifically targeted to EGFR-overexpressing cancer cells using GE11 peptide ligands, to enhance cell-specific Pc 4 delivery and internalization. In the current study, we report on the in vitro optimization of the EGFR-targeting, Pc 4 loading of the micellar nanoformulation, along with optimization of the corresponding photoirradiation conditions to maximize Pc 4 delivery, internalization, and subsequent PDT-induced cytotoxicity in EGFR-overexpressing cells in vitro. In our studies, absorption and fluorescence spectroscopy were used to monitor the cell-specific uptake of the GE11-decorated Pc 4-loaded micelles and the cytotoxic singlet oxygen production from the micelle-encapsulated Pc 4, to determine the optimum ligand density and Pc 4 loading. It was found that the micelle formulations bearing 10 mol % of GE11-modified polymer component resulted in the highest cellular uptake in EGFR-overexpressing A431 cells within the shortest incubation periods. Also, the loading of ∼ 50 μg of Pc 4 per mg of polymer in these micellar formulations resulted in the highest levels of singlet oxygen production. When formulations bearing these optimized parameters were tested in vitro on A431 cells for PDT effect, a formulation dose containing 400 nM Pc 4 and photoirradiation duration of 400 s at a fluence of 200 mJ/cm(2) yielded close to 100% cell death.
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Affiliation(s)
- Alyssa M Master
- Department of Biomedical Engineering, Case Western Reserve University, 2071 Martin Luther King Drive, Cleveland, Ohio 44106, United States
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Soares ARM, Neves MGPMS, Tomé AC, Iglesias-de la Cruz MC, Zamarrón A, Carrasco E, González S, Cavaleiro JAS, Torres T, Guldi DM, Juarranz A. Glycophthalocyanines as Photosensitizers for Triggering Mitotic Catastrophe and Apoptosis in Cancer Cells. Chem Res Toxicol 2012; 25:940-51. [DOI: 10.1021/tx300035a] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Ana R. M. Soares
- Universidade de Aveiro, Departamento de Química, QOPNA, 3810-193
Aveiro, Portugal
- Departamento
de Química
Orgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, IMDEA Nanociencia, Cantoblanco 28049 Madrid,
Spain
| | | | - Augusto C. Tomé
- Universidade de Aveiro, Departamento de Química, QOPNA, 3810-193
Aveiro, Portugal
| | | | - Alicia Zamarrón
- Departamento de Biología,
Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco 28049, Madrid, Spain
| | - Elisa Carrasco
- Departamento de Biología,
Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco 28049, Madrid, Spain
| | - Salvador González
- Dermatology Service, Memorial Sloan-Kettering Cancer Center, New York, United
States
| | - José A. S. Cavaleiro
- Universidade de Aveiro, Departamento de Química, QOPNA, 3810-193
Aveiro, Portugal
| | - Tomás Torres
- Departamento
de Química
Orgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, IMDEA Nanociencia, Cantoblanco 28049 Madrid,
Spain
| | - Dirk M. Guldi
- Friedrich-Alexander-Universität Erlangen-Nürnberg, Department of Chemistry and Pharmacy & Interdisciplinary Center for Molecular Materials (ICMM), 91058, Erlangen, Germany
| | - Angeles Juarranz
- Departamento de Biología,
Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco 28049, Madrid, Spain
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