Conti Florencia Silvina, Giorgi Exequiel, Montaldo Laura, Rodríguez Juan Pablo, De Marzi Mauricio Cesar, Baudou Federico Gastón
Grupo de Investigaciones Básicas y Aplicadas en Inmunología y Bioactivos (GIBAIB, INEDES-CONICET), Departamento de Ciencias Básicas, Universidad Nacional de Luján (UNLu), Luján C6700, Argentina.
FOCIS Center of Excellence-Vaccines and Immuno Therapies Against Infections and Cancers (VITIC), Menomonee Falls, WI 53051, USA.
Pharmaceutics. 2025 Jul 4;17(7):879. doi: 10.3390/pharmaceutics17070879.
: Ophidism is a globally neglected health problem. In Argentina, (., South American rattlesnake) is one of the species of greatest medical importance since its venom contains mainly crotoxin (CTX), a potent enzyme-toxin with PLA activity, which is responsible for its high lethality. : In this work, we aimed to generate nanovenoms (NVs), complexes formed by CTX adsorbed onto 150 nm silica nanoparticles (SiNPs), and to study their physicochemical, biological, and immunomodulatory activities for potential use as adjuvants (ADJs) in antivenom (AV) production. : CTX was isolated and corroborated by SDS-PAGE. Then, CTX was adsorbed on the synthetized Stöber SiNPs' surfaces, forming a monolayer and retaining its biological activity (as observed by the MTT cell proliferation assay using the THP-1 cell line). : Immunomodulatory activity revealed a high pro-inflammatory (IL-1β) response induced by SiNPs followed by NVs. In the case of the anti-inflammatory response, NVs presented significant differences for TGF-β only after cell activation with LPS. No significant differences were observed in IL-10 levels. : Thus, these results suggest that NVs together with SiNPs could increase immunogenicity and enhance immune response, turning them into potential tools for the generation of new antivenoms.
蛇咬伤中毒是一个全球范围内被忽视的健康问题。在阿根廷,(例如,南美响尾蛇)是具有最重要医学意义的物种之一,因为其毒液主要含有巴曲毒素(CTX),这是一种具有磷脂酶A活性的强效酶毒素,其高致死率与此有关。:在这项工作中,我们旨在制备纳米毒液(NVs),即由吸附在150纳米二氧化硅纳米颗粒(SiNPs)上的CTX形成的复合物,并研究它们的物理化学、生物学和免疫调节活性,以潜在地用作抗蛇毒血清(AV)生产中的佐剂(ADJs)。:通过SDS-PAGE分离并确证了CTX。然后,将CTX吸附在合成的施托伯SiNPs表面,形成单层并保留其生物活性(如使用THP-1细胞系的MTT细胞增殖试验所观察到的)。:免疫调节活性显示,SiNPs随后是NVs诱导了高促炎(IL-1β)反应。在抗炎反应方面,仅在用LPS激活细胞后,NVs在TGF-β方面呈现出显著差异。在IL-10水平上未观察到显著差异。:因此,这些结果表明,NVs与SiNPs一起可以增加免疫原性并增强免疫反应,使其成为生成新型抗蛇毒血清的潜在工具。