Photoinduced Photosensitizer-Antibody Conjugates Kill HIV Env-Expressing Cells, Also Inactivating HIV

Mohammad Sadraeian; Edgar Ferreira da Cruz; Ross W Boyle; Calise Bahou; Vijay Chudasama; Luiz Mário Ramos Janini; Ricardo Sobhie Diaz; Francisco E G Guimarães

doi:10.1021/acsomega.1c01721

Photoinduced Photosensitizer-Antibody Conjugates Kill HIV Env-Expressing Cells, Also Inactivating HIV

ACS Omega. 2021 Jun 8;6(25):16524-16534. doi: 10.1021/acsomega.1c01721. eCollection 2021 Jun 29.

Authors

Mohammad Sadraeian¹, Edgar Ferreira da Cruz², Ross W Boyle³, Calise Bahou⁴, Vijay Chudasama⁴, Luiz Mário Ramos Janini², Ricardo Sobhie Diaz², Francisco E G Guimarães¹

Affiliations

¹ São Carlos Institute of Physics, University of São Paulo, Caixa Postal 369, São Carlos, SP CEP 13560-970, Brazil.
² Laboratório de Retrovirologia, Universidade Federal de São Paulo, São Paulo, Brazil.
³ Department of Chemistry, University of Hull, Cottingham Road, Hull HU6 7RX, U.K.
⁴ Department of Chemistry, University College London, London WC1H 0AJ, U.K.

Abstract

HIV-infected cells persist for decades in patients administered with antiretroviral therapy (ART). Meanwhile, an alarming surge in drug-resistant HIV viruses has been occurring. Addressing these issues, we propose the application of photoimmunotherapy (PIT) against not only HIV Env-expressing cells but also HIV. Previously, we showed that a human anti-gp41 antibody (7B2) conjugated to cationic or anionic photosensitizers (PSs) could specifically target and kill the HIV Env-expressing cells. Here, our photolysis studies revealed that the binding of photoimmunoconjugates (PICs) on the membrane of HIV Env-expressing cells is sufficient to induce necrotic cell death due to physical damage to the membrane by singlet oxygen, which is independent of the type of PSs. This finding persuaded us to study the virus photoinactivation of PICs using two HIV-1 strains, X4 HIV-1 NL4-3 and JR-CSF virus. We observed that the PICs could destroy the viral strains, probably via physical damage on the HIV envelope. In conclusion, we report the application of PIT as a possible dual-tool for HIV immunotherapy and ART by killing HIV-expressing cells and cell-free HIV, respectively.