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Cell influx\/efflux studies in Caco-2 cells suggest that YAT2150 is internalized by endocytosis and also through the OATP2B1 transporter, whereas its main export route would be via OST\u03b1. YAT2150 has an overall favorable drug metabolism and pharmacokinetics profile, and its moderate cytotoxicity can be significantly reduced upon encapsulation in immunoliposomes, which leads to a dramatic increase in the drug selectivity index to values close to 1000. Although YAT2150 binds amyloid-forming peptides, its in vitro fluorescence emission is stronger upon association with peptides that form amorphous aggregates, suggesting that regions enriched in unstructured proteins are the preferential binding sites of the drug inside Plasmodium cells. The reduction of protein aggregation in the parasite after YAT2150 treatment, which has been suggested to be directly related to the drug\u2019s mode of action, is also observed following treatment with quinoline antimalarials like chloroquine and primaquine. Conclusions: Altogether, the data presented here indicate that YAT2150 can represent the spearhead of a new family of compounds for malaria diagnosis and therapy due to its presumed novel mode of action based on the interaction with functional protein aggregates in the pathogen.<\/jats:p>","DOI":"10.3390\/pharmaceutics16101290","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T03:57:52Z","timestamp":1727755072000},"page":"1290","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1101-7758","authenticated-orcid":false,"given":"Claudia","family":"Camarero-Hoyos","sequence":"first","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), Hospital Cl\u00ednic-Universitat de Barcelona, Rossell\u00f3 149-153, 08036 Barcelona, Spain"},{"name":"Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology, Baldiri Reixac 10-12, 08028 Barcelona, Spain"},{"name":"Doctoral School of Biotechnology, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. 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