Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells

Author(s)

Sadraeian, Mohammad ^{[1, 2]} ; Bahou, Calise ^[3] ; da Cruz, Edgar Ferreira ^[4] ; Ramos Janini, Luiz Mario ^[4] ; Diaz, Ricardo Sobhie ^[4] ; Boyle, Ross W. ^[5] ; Chudasama, Vijay ^[3] ; Gontijo Guimaraes, Francisco Eduardo ^[1]

Affiliation

^[1] Univ Sao Paulo, Sao Carlos Inst Phys, BR-13566590 Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, Caixa Postal 369, BR-13566590 Sao Carlos, SP - Brazil

^[3] UCL, Dept Chem, London WC1H 0AJ - England

^[4] Univ Fed Sao Paulo, Dept Microbiol Imunol Parasitol, Lab Retrovirol, Disciplina Microbiol, BR-04039032 Sao Paulo, SP - Brazil

^[5] Univ Hull, Dept Chem, Cottingham Rd, Kingston Upon Hull HU6 7RX, N Humberside - England

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 21, n. 23 DEC 2020.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 13/07276-1 - CEPOF - Optics and Photonic Research Center
• Grantee: Vanderlei Salvador Bagnato
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/10910-5 - Production and Characterization of Novel Photoimmunoconjugates for HIV Photoimmunotherapy
• Grantee: Mohammad Sadraeian
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/54035-4 - Facility for advanced studies of biosystems and nanostructured materials
• Grantee: Igor Polikarpov
• Support Opportunities: Multi-user Equipment Program