Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells
Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/9151 |
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| author | Mohammad Sadraeian Calise Bahou Edgar Ferreira da Cruz Luíz Mário Ramos Janini Ricardo Sobhie Diaz Ross W. Boyle Vijay Chudasama Francisco Eduardo Gontijo Guimarães |
| author_facet | Mohammad Sadraeian Calise Bahou Edgar Ferreira da Cruz Luíz Mário Ramos Janini Ricardo Sobhie Diaz Ross W. Boyle Vijay Chudasama Francisco Eduardo Gontijo Guimarães |
| author_sort | Mohammad Sadraeian |
| collection | DOAJ |
| description | Different therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers (PSs) with different charges through different linking strategies; “Click” conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and “Lysine” conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells. |
| first_indexed | 2024-03-10T14:25:12Z |
| format | Article |
| id | doaj.art-6090887ba56841be83d8dc14e41ea209 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:25:12Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6090887ba56841be83d8dc14e41ea2092023-11-20T23:04:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012123915110.3390/ijms21239151Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing CellsMohammad Sadraeian0Calise Bahou1Edgar Ferreira da Cruz2Luíz Mário Ramos Janini3Ricardo Sobhie Diaz4Ross W. Boyle5Vijay Chudasama6Francisco Eduardo Gontijo Guimarães7São Carlos Institute of Physics, University of São Paulo, São Carlos, SP 13566-590, BrazilDepartment of Chemistry, University College London, London WC1H 0AJ, UKLaboratório de Retrovirologia, Disciplina de Microbiologia, Departamento de Microbiologia Imunologia Parasitologia, Universidade Federal de São Paulo, São Paulo, SP 04039-032, BrazilLaboratório de Retrovirologia, Disciplina de Microbiologia, Departamento de Microbiologia Imunologia Parasitologia, Universidade Federal de São Paulo, São Paulo, SP 04039-032, BrazilLaboratório de Retrovirologia, Disciplina de Microbiologia, Departamento de Microbiologia Imunologia Parasitologia, Universidade Federal de São Paulo, São Paulo, SP 04039-032, BrazilDepartment of Chemistry, University of Hull, Cottingham Road, Hull HU6 7RX, UKDepartment of Chemistry, University College London, London WC1H 0AJ, UKSão Carlos Institute of Physics, University of São Paulo, São Carlos, SP 13566-590, BrazilDifferent therapeutic strategies have been investigated to target and eliminate HIV-1-infected cells by using armed antibodies specific to viral proteins, with varying degrees of success. Herein, we propose a new strategy by combining photodynamic therapy (PDT) with HIV Env-targeted immunotherapy, and refer to it as HIV photoimmunotherapy (PIT). A human anti-gp41 antibody (7B2) was conjugated to two photosensitizers (PSs) with different charges through different linking strategies; “Click” conjugation by using an azide-bearing porphyrin attached via a disulfide bridge linker with a drug-to-antibody ratio (DAR) of exactly 4, and “Lysine” conjugation by using phthalocyanine IRDye 700DX dye with average DARs of 2.1, 3.0 and 4.4. These photo-immunoconjugates (PICs) were compared via biochemical and immunological characterizations regarding the dosimetry, solubility, and cell targeting. Photo-induced cytotoxicity of the PICs were compared using assays for apoptosis, reactive oxygen species (ROS), photo-cytotoxicity, and confocal microscopy. Targeted phototoxicity seems to be primarily dependent on the binding of PS-antibody to the HIV antigen on the cell membrane, whilst being independent of the PS type. This is the first report of the application of PIT for HIV immunotherapy by killing HIV Env-expressing cells.https://www.mdpi.com/1422-0067/21/23/9151HIV immunotherapyphotoimmunotherapyphotodynamic therapyporphyrinphthalocyanineHIV-infected cell |
| spellingShingle | Mohammad Sadraeian Calise Bahou Edgar Ferreira da Cruz Luíz Mário Ramos Janini Ricardo Sobhie Diaz Ross W. Boyle Vijay Chudasama Francisco Eduardo Gontijo Guimarães Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells International Journal of Molecular Sciences HIV immunotherapy photoimmunotherapy photodynamic therapy porphyrin phthalocyanine HIV-infected cell |
| title | Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells |
| title_full | Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells |
| title_fullStr | Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells |
| title_full_unstemmed | Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells |
| title_short | Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells |
| title_sort | photoimmunotherapy using cationic and anionic photosensitizer antibody conjugates against hiv env expressing cells |
| topic | HIV immunotherapy photoimmunotherapy photodynamic therapy porphyrin phthalocyanine HIV-infected cell |
| url | https://www.mdpi.com/1422-0067/21/23/9151 |
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