Multiepitope glycan based laser assisted fluorescent nanocomposite with dual functionality for sensing and ablation of Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa (P. aeruginosa) infection is becoming a severe health hazard and needs early diagnosis with high specificity. However, the non-specific binding of a biosensor is a challenge to the current bacterial detection system. For the first time, we chemically synthesized a galactose tripod (GT) as a P. aeruginosa-specific ligand. We conjugated GT to a photothermally active fluorescent nanocomposite (Au@SiO₂-TCPP). P. aeruginosa can be detected using Au@SiO₂-TCPP-GT, and additionally ablated as well using synergistic photothermal and photodynamic therapy. Molecular dynamics and simulation studies suggested better binding of GT (binding energy = −6.6 kcal mol⁻¹) with P. aeruginosa lectin than that of galactose monopod (GM) (binding energy = −5.9 kcal mol⁻¹). Furthermore, a binding study was extended to target P. aeruginosa, which has a galactose-binding carbohydrate recognition domain receptor. The colorimetric assay confirmed a limit of detection (LOD) of 10⁴ CFU mL⁻¹. We also looked into the photosensitizing property of Au@SiO₂-TCPP-GT, which is stimulated by laser light (630 nm) and causes photoablation of bacteria by the formation of singlet oxygen in the surrounding media. The cytocompatibility of Au@SiO₂-TCPP-GT was confirmed using cytotoxicity assays on mammalian cell lines. Moreover, Au@SiO₂-TCPP-GT also showed non-hemolytic activity. Considering the toxicity analysis and efficacy of the synthesized glycan nanocomposites, these can be utilized for the treatment of P. aeruginosa-infected wounds. Furthermore, the current glycan nanocomposites can be used for bacterial detection and ablation of P. aeruginosa in contaminated food and water samples as well.