Developing nanomaterials-based targeted theranostic applications against parasitic infections using Acanthamoeba as a model organism

Infections caused by free-living amoebae are increasing worldwide, yet therapeutic options remain severely limited and frequently ineffective. Among these pathogens, Acanthamoeba spp. are implicated in severe eye infections such as Acanthamoeba keratitis (AK), a leading cause of vision loss and blindness, and granulomatous amoebic encephalitis (GAE), a rare but lethal brain infection marked by high morbidity and mortality when diagnosis and treatment are delayed. AK represents a major clinical challenge owing to its rapid progression, excruciating pain, and risk of permanent vision loss, affecting contact lens wearers. The resilience of Acanthamoeba, particularly its ability to form highly resistant cysts, underscores the urgent need for novel agents that can target both trophozoites and cysts. Plant-derived natural products have emerged as promising candidates due to their diverse bioactivity and favourable safety profiles. In this study, the anti-Acanthamoeba potential of vanillic acid, delivered via an innovative carrier system composed of iron, copper, and xanthan gum, was investigated. The formulated vanillic acid was evaluated against Acanthamoeba castellanii, including trophozoite viability and growth inhibition, encystation and excystation blockade, morphological assessment, and cytotoxicity towards mammalian cells. Results demonstrated potent amoebicidal and amoebistatic activity with the formulated vanillic acid, achieving significant reduction in trophozoite viability, inhibition of encystation and excystation, and pronounced morphological disruption. Significantly, the formulation exhibited negligible cytotoxicity against human cells at therapeutically relevant concentrations. These findings highlight vanillic acid, when optimised through a metal–polymer carrier system, as a promising and safe candidate for the development of new therapeutic strategies against Acanthamoeba infections.