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

Autor: Sadraeian M; São Carlos Institute of Physics, University of São Paulo, Caixa Postal 369, São Carlos, SP CEP 13560-970, Brazil., da Cruz EF; Laboratório de Retrovirologia, Universidade Federal de São Paulo, São Paulo, Brazil., Boyle RW; Department of Chemistry, University of Hull, Cottingham Road, Hull HU6 7RX, U.K., Bahou C; Department of Chemistry, University College London, London WC1H 0AJ, U.K., Chudasama V; Department of Chemistry, University College London, London WC1H 0AJ, U.K., Janini LMR; Laboratório de Retrovirologia, Universidade Federal de São Paulo, São Paulo, Brazil., Diaz RS; Laboratório de Retrovirologia, Universidade Federal de São Paulo, São Paulo, Brazil., Guimarães FEG; São Carlos Institute of Physics, University of São Paulo, Caixa Postal 369, São Carlos, SP CEP 13560-970, Brazil.
Jazyk: angličtina
Zdroj: ACS omega [ACS Omega] 2021 Jun 08; Vol. 6 (25), pp. 16524-16534. Date of Electronic Publication: 2021 Jun 08 (Print Publication: 2021).
DOI: 10.1021/acsomega.1c01721
Abstrakt: 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.
Competing Interests: The authors declare the following competing financial interest(s): V.C. is a Director of ThioLogics. Other authors declare no competing interests.
(© 2021 The Authors. Published by American Chemical Society.)
Databáze: MEDLINE