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

Sadraeian, M; Bahou, C; da Cruz, EF; Janini, LMR; Sobhie Diaz, R; Boyle, RW; Chudasama, V; Eduardo Gontijo Guimarães, F

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

Sadraeian, M

Bahou, C da Cruz, EF Janini, LMR Sobhie Diaz, R Boyle, RW Chudasama, V Eduardo Gontijo Guimarães, F

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Publisher:: MDPI
Publication Type:: Journal Article
Citation:: Int J Mol Sci, 2020, 21, (23), pp. E9151
Issue Date:: 2020-12-01

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Field	Value	Language
dc.contributor.author	Sadraeian, M https://orcid.org/0000-0002-7384-2247
dc.contributor.author	Bahou, C
dc.contributor.author	da Cruz, EF
dc.contributor.author	Janini, LMR
dc.contributor.author	Sobhie Diaz, R
dc.contributor.author	Boyle, RW
dc.contributor.author	Chudasama, V
dc.contributor.author	Eduardo Gontijo Guimarães, F
dc.date.accessioned	2022-10-30T19:14:35Z
dc.date.available	2020-11-21
dc.date.available	2022-10-30T19:14:35Z
dc.date.issued	2020-12-01
dc.identifier.citation	Int J Mol Sci, 2020, 21, (23), pp. E9151
dc.identifier.issn	1422-0067
dc.identifier.issn	1422-0067
dc.identifier.uri	http://hdl.handle.net/10453/162945
dc.description.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.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI
dc.relation.ispartof	Int J Mol Sci
dc.relation.isbasedon	10.3390/ijms21239151
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0399 Other Chemical Sciences, 0604 Genetics, 0699 Other Biological Sciences
dc.subject.classification	Chemical Physics
dc.subject.mesh	Anions
dc.subject.mesh	Anti-HIV Agents
dc.subject.mesh	Antibodies, Monoclonal
dc.subject.mesh	Apoptosis
dc.subject.mesh	Cations
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Cells, Cultured
dc.subject.mesh	Flow Cytometry
dc.subject.mesh	Fluorescent Antibody Technique
dc.subject.mesh	HIV
dc.subject.mesh	HIV Infections
dc.subject.mesh	Humans
dc.subject.mesh	Immunoconjugates
dc.subject.mesh	Photochemotherapy
dc.subject.mesh	Photosensitizing Agents
dc.subject.mesh	Reactive Oxygen Species
dc.subject.mesh	Virus Replication
dc.subject.mesh	env Gene Products, Human Immunodeficiency Virus
dc.subject.mesh	Cells, Cultured
dc.subject.mesh	Cell Line, Tumor
dc.subject.mesh	Humans
dc.subject.mesh	HIV
dc.subject.mesh	HIV Infections
dc.subject.mesh	Anions
dc.subject.mesh	Cations
dc.subject.mesh	Reactive Oxygen Species
dc.subject.mesh	Photosensitizing Agents
dc.subject.mesh	Antibodies, Monoclonal
dc.subject.mesh	Immunoconjugates
dc.subject.mesh	Anti-HIV Agents
dc.subject.mesh	Fluorescent Antibody Technique
dc.subject.mesh	Photochemotherapy
dc.subject.mesh	Flow Cytometry
dc.subject.mesh	Virus Replication
dc.subject.mesh	Apoptosis
dc.subject.mesh	env Gene Products, Human Immunodeficiency Virus
dc.title	Photoimmunotherapy Using Cationic and Anionic Photosensitizer-Antibody Conjugates against HIV Env-Expressing Cells.
dc.type	Journal Article
utslib.citation.volume	21
utslib.location.activity	Switzerland
utslib.for	0399 Other Chemical Sciences
utslib.for	0604 Genetics
utslib.for	0699 Other Biological Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access	*
dc.date.updated	2022-10-30T19:14:18Z
pubs.issue	23
pubs.publication-status	Published online
pubs.volume	21
utslib.citation.issue	23

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.

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http://hdl.handle.net/10453/162945