Nanomalaria

Main research lines of the Nanomalaria group:

• Definition of polymeric nanocarriers which combine into a single chemical structure drug encapsulating capacity, antiplasmodial activity, specific targeting to Plasmodium-infected red blood cells (pRBCs), and affordable synthesis cost. This line of research is currently being adapted to develop new nanomedicines for leishmaniasis.
• Application of heparin as a dual agent with antimalarial and nanovector targeting activities toward pRBCs.
• Targeting Plasmodium stages in the mosquito vector, which will bypass long and costly clinical trials that often delay or prevent the development of nanomedicines for malaria.
• Use of red blood cells (RBCs) as antimalarial carriers, an innovative strategy that confronts Plasmodium with drugs at the moment of erythrocyte infection by the pathogen. Using this approach that provided excellent in vivo results where malaria-infected mice were freed of parasites and cured, we have developed new immunoliposomes carrying drug combinations for their targeted delivery to RBCs and gametocytes, the transmission stage shared between humans and the Anopheles mosquito vector which is a preferred target of malaria eradication efforts.
• Development of DNA aptamers as new malaria diagnostic agents.
• Identification, cloning and characterization of the proteins mediating vesicular transport in Plasmodium, using nanotechnological femtoinjection techniques in giant unilamellar vesicles.
• Discovery of functional protein aggregation in live Plasmodium and Leishmania parasites, and of a new family of drugs targeting this process.

Projects

• 2023-2026: Research grant, CaixaResearch Health Call 2023. Project title: “Compact Analytical Tool for robust MALaria decentralized diagnosis and community surveillance.” (LCF/PR/HR23/52430013). 01/12/2023 - 30/11/2026.
• 2024-2027: Research grant, CaixaResearch Health Call 2024. Project title: “Protein Aggregation in the Malaria PArasite: WHAT for?” (LCF/PR/HR24/52440003). 01/12/2024 - 30/11/2027.
• 2025-2028: Research grant, Ministerio de Ciencia, Innovación y Universidades, Spain. Project title: “YAT2150: elucidation of its targets and their validation in Leishmania.” (PID2024-156230OB-I00). 01/09/2025 - 31/08/2028.

With the support of:

Selected Publications

• Avalos-Padilla Y, Bouzón-Arnáiz I, Ramírez M, Camarero-Hoyos C, Orozco-Quer M, M Arce E, Muñoz-Torrero D, Fernàndez-Busquets X. Overexpression in Plasmodium falciparumof an intrinsically disordered protein segment of PfUT impairs the parasite's proteostasis and reduces its growth rate. Front Cell Infect Microbiol. 2025 May 13;15:1565814. doi: 10.3389/fcimb.2025.1565814.
• Bouzón-Arnáiz I, Rawat M, Coyle R, Feufack-Donfack LB, Ea M, Orban A, Popovici J, Román-Álamo L, Fallica AN, Domínguez-Asenjo B, Moreno J, Arce EM, Mallo-Abreu A, Muñoz-Torrero D, Lee MCS, Fernàndez-Busquets X. YAT2150 is irresistible in Plasmodium falciparum and active against Plasmodium vivax and Leishmania clinical isolates. Sci Rep. 2025 Jan 23;15(1):2941. doi: 10.1038/s41598-025-85346-y.
• Camarero-Hoyos C, Bouzón-Arnáiz I, Avalos-Padilla Y, Fallica AN, Román-Álamo L, Ramírez M, Portabella E, Cuspinera O, Currea-Ayala D, Orozco-Quer M, Ribera M, Siden-Kiamos I, Spanos L, Iglesias V, Crespo B, Viera S, Andreu D, Sulleiro E, Zarzuela F, Urtasun N, Pérez-Torras S, Pastor-Anglada M, Arce EM, Muñoz-Torrero D, Fernàndez-Busquets X. Leveraging the Aggregated Protein Dye YAT2150 for Malaria Chemotherapy. Pharmaceutics. 2024 Sep 30;16(10):1290. doi: 10.3390/pharmaceutics16101290.
• Román-Álamo L, Avalos-Padilla Y, Bouzón-Arnáiz I, Iglesias V, Fernández-Lajo J, Monteiro JM, Rivas L, Fisa R, Riera C, Andreu D, Pintado-Grima C, Ventura S, Arce EM, Muñoz-Torrero D, Fernàndez-Busquets X. Effect of the aggregated protein dye YAT2150 on Leishmaniaparasite viability. Antimicrob Agents Chemother. 2024 Mar 6;68(3):e0112723. doi: 10.1128/aac.01127-23.
• San Anselmo M, Lantero E, Avalos-Padilla Y, Bouzón-Arnáiz I, Ramírez M, Postigo A, Serrano JL, Sierra T, Hernández-Ainsa S, Fernàndez-Busquets X. Heparin-Coated Dendronized Hyperbranched Polymers for Antimalarial Targeted Delivery. ACS Appl Polym Mater. 2022 Dec 30;5(1):381-390. doi: 10.1021/acsapm.2c01553.
• Bouzón-Arnáiz I, Avalos-Padilla Y, Biosca A, Caño-Prades O, Román-Álamo L, Valle J, Andreu D, Moita D, Prudêncio M, Arce EM, Muñoz-Torrero D, Fernàndez-Busquets X. The protein aggregation inhibitor YAT2150 has potent antimalarial activity in Plasmodium falciparum in vitro cultures. BMC Biol. 2022 Oct 22;20(1):197. doi: 10.1186/s12915-022-01374-4.
• Avalos-Padilla Y, Georgiev VN, Lantero E, Pujals S, Verhoef R, Borgheti-Cardoso LN, Albertazzi L, Dimova R, Fernàndez-Busquets X. The ESCRT-III machinery participates in the production of extracellular vesicles and protein export during Plasmodium falciparum infection. PLoS Pathog. 2021 17:e1009455. doi: 10.1371/journal.ppat.1009455.
• Biosca, A, Cabanach, P, Abdulkarim, M, Gumbleton, M, Gómez-Canela, C, Ramírez, M, Bouzón-Arnáiz, I, Avalos-Padilla, Y, Borros, S, and Fernàndez-Busquets, X (2021) Zwitterionic self-assembled nanoparticles as carriers for Plasmodium targeting in malaria oral treatment. J. Control. Release 331, 364-375. doi: 10.1016/j.jconrel.2021.01.028.
• Biosca, A, Bouzón-Arnáiz, I, Spanos, L, Siden-Kiamos, I, Iglesias, V, Ventura, S, and Fernàndez-Busquets, X (2020) Detection of protein aggregation in live Plasmodiumparasites. Antimicrob. Agents Chemother. 64, e02135-19. doi: 10.1128/AAC.02135-19.
• Patent: Compounds for the treatment of malaria. Inventors: Fernàndez-Busquets X, Biosca A, Bouzón-Arnáiz I, Muñoz-Torrero D, Martínez-Arce E, Reolid-Coll P. Institutions (titular entity in bold): IBEC, ISGlobal, Universitat de Barcelona. European patent number: EP21382949.2; priority countries, date: Europe, 21/10/2021. Application number: PCT/EP2022/079438; application date: 21/10/22.