Sialic Acid and Colchicine Functionalized Silica Nanoparticles: A Novel Approach to Leishmanicidal Selective Treatments Galue Parra, Adán Jesús Jiménez-Falcao, Sandra Arribas Yuste, Esther Marín Sánchez, Clotilde Méndez Arriaga, José Manuel parasite Leishmania neglected diseases sialic acid Colchicine Drug delivery Nanoparticle Background/Objectives: Leishmaniasis remains a neglected tropical disease, with nearly one million new cases annually and limited investment in research. Current treatments, primarily based on pentavalent antimonials, are associated with severe side effects and increasing resistance. This study aims to develop a novel therapeutic strategy using a nanomaterial functionalized with sialic acid (SA) and colchicine (COL) to selectively target Leishmania braziliensis parasites. Methods: A nanostructured system was engineered by functionalizing its surface with SA and COL. SA was chosen to mimic host cell surfaces, enhancing parasite attraction, while COL was selected for its known leishmanicidal properties. The nanomaterial was designed to concentrate extracellular parasites on its surface via SAmediated interactions, thereby increasing local COL efficacy. Results: The functionalized nanomaterial demonstrated a dual mechanism: SA facilitated the selective accumulation of Leishmania braziliensis parasites on the nanostructure surface, while COL exerted a cytotoxic effect. This synergistic interaction resulted in enhanced parasite mortality in vitro, suggesting improved selectivity and potency compared to conventional treatments. Conclusions: The proposed nanomaterial offers a promising alternative for leishmaniasis treatment by combining targeted parasite attraction with localized drug delivery. This strategy may reduce systemic toxicity and improve therapeutic outcomes. 2025-07-24T10:09:23Z 2025-07-24T10:09:23Z 2025-07-06 journal article Galue-Parra, A.J.; Jimenez-Falcao, S.; Arribas-Yuste, E.; Marin, C.; Mendez-Arriaga, J.M. Sialic Acid and Colchicine Functionalized Silica Nanoparticles: A Novel Approach to Leishmanicidal Selective Treatments. Biomedicines 2025, 13, 1648. https://doi.org/10.3390/ biomedicines13071648 https://hdl.handle.net/10481/105624 10.3390/ biomedicines13071648 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI