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journal article·2025-08Open access

Fast pH‐Driven Solubilization Method of Realgar (As 4 S 4 ) to Reduce the Toxicity of Arsenic [As(III)] for Medicinal Purposes

Bojana Lucic, Douglas Santana Franciscato, Helton Pereira Nogueira, Lara Gallucci, Alceu Totti Silveira Junior, Asmaa Mohamed Ismail, Millie Robinson, Teresa Dallinger, Claudia Gutfleisch, Jochen Kurz, Maytê Toledo, Jessica Dias da Silva Ferraz, Mohammad Tarek, Danilo Dias, Ricardo Sobhie Diaz, Mahmoud ElHefnawi, Mattia Forcato, Hugo P Monteiro, Marina Lusic, Iart Luca Shytaj, Andrea Savarino

Advanced Science· Volume 12· Issue 29
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Abstract

Abstract Acute promyelocytic leukemia (APL) accounts for 5–15% of acute myeloid leukemia cases. It is typically characterized by the (15;17) chromosomal translocation, producing the pathogenic retinoic acid receptor (RAR) alpha/promyelocytic leukemia (PML) fusion protein. Recently, remission of APL has been achieved using the first chemotherapy‐independent oral drug regimen in anticancer therapy, consisting of all‐trans retinoic acid (targeting RARalpha) and the arsenic sulfide realgar (targeting PML). However, clinical adoption of realgar and the characterization of its active breakdown products have been hampered by its poor solubility. Here, a scalable pH/temperature‐based process is described that partially mimics gut transition, achieving fast and reproducible solubilization of realgar. Six different spectroscopic and spectrometric techniques are employed to investigate solubilized realgar. Furthermore, it is shown that solubilized realgar targets PML, displaying wider in vitro therapeutic indices and lower off‐target effects than arsenic trioxide, the current APL standard of care. Moreover, in line with evidence of an interplay between PML and HIV persistence, solubilized realgar can disrupt HIV latency, the main barrier to an HIV/AIDS cure, in CD4 T cells of people living with HIV. These findings may open avenues for streamlining realgar solubilization and designing less toxic, orally administrable arsenic‐based therapies.
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Research context

OpenAlex topics: Arsenic contamination and mitigation · Pregnancy and Medication Impact · Selenium in Biological Systems

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Infectious Diseases Integrative Virology Heidelberg University 69120 Heidelberg Germany

German Center for Infection Research 69120 Heidelberg Germany

Institute of Chemistry University of São Paulo São Paulo 05508‐220 Brazil

School of Cellular and Molecular Medicine University of Bristol Bristol BS8 1TD UK

Spectroscopy Department National Research Centre 33 El Bohouth Street Dokki Giza 12622 Egypt

Center for Infectious Diseases Medical Microbiology und Hygiene University Hospital Heidelberg 69120 Heidelberg Germany

Department of Biochemistry Center for Cellular and Molecular Therapy Federal University of São Paulo São Paulo 04021‐001 Brazil

Infectious Diseases Department Federal University of São Paulo São Paulo 04021‐001 Brazil

Clinical Hematology Department Armed Forces College of Medicine (AFCM) Cairo Governatorate Heliopolis 11774 Egypt

Informatics and Systems Department National Research Centre 33 El Bohouth Street, Dokki Giza 12622 Egypt

Department of Molecular Medicine University of Padova Padova 35122 Italy

Department of Infectious Diseases Italian Institute of Health Rome 00161 Italy

Funding

Medical Research Council · Deutsche Forschungsgemeinschaft · Deutsches Zentrum für Infektionsforschung · Fundação de Amparo à Pesquisa do Estado de São Paulo · Engineering and Physical Sciences Research Council

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