Fast pH‐Driven Solubilization Method of Realgar (As 4 S 4 ) to Reduce the Toxicity of Arsenic [As(III)] for Medicinal Purposes
Year: 2025
Type: article
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.
Source: Advanced Science
Authors: 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
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,730
Awards: Integrating subcellular multi-omics to identify druggable metabolic markers of latent HIV infection in CD4 T-cells, G2749423176, Ex Vivo Profiling and Targeting of Metabolic Dysregulation in HIV-1 Infected Lymph Node Organoids., G3842438612, Aufklärung des epigenetischen und metabolischen Zusammenspiels in der Übergangsphase zwischen Zellschicksalen von HIV1infizierten TZellen, Multiple interventions to eliminate HIV reservoirs among antiretroviral treated individuals in order to obtain sustained HIV remission without antiretrovirals, Tumor development under the perspective of redox signaling: temporal modulation of the production of nitric oxide and reactive oxygen species, G7921036304
OpenAlex ID: W4409733919