Gold nanoparticles (AuNPs) are of great interest because of their tolerable in vivo toxicity, unique optical properties, good resistance to oxidation and ease of surface functionalization. Among the bioaffinity based approaches to functionalize AuNPs surface in accordance with the target and application, decoration with carbohydrates specific to lectins of the target cells is promising owing to the specificity and sensitivity of carbohydrate-lectin interactions. However, the current state of carbohydrate-decorated AuNPs are far from practical biological applications. In this study, a variety of monosaccharides and disaccharides including D-/L- Mannose, D-galactose, D-xylose and D-sucrose were modified with phenylene-amine derivatives for one-pot synthesis of chiral AuNP glycoconjugates (AuNP-GC). Surface of the AuNP-GCs were then further enhanced with D-amino acids and bioactive molecules. Selective toxicity of the AuNP-GCs on lung and liver cancer cells (e.g. A549, HepG2 etc) in comparison to the non-cancerous cells (e.g. CCD-LU34 cells) showed strong dependence on the sugar ligands and their chirality. Similarly, sugar ligands and their chirality showed strong effect for the observed toxicity towards the tested 18 different bacteria (e.g. E.coli, L.monocytogenes and drug resistant S.aureus) . D-amino acids (e.g. cysteine) and biomolecule (glutathione) brought further selective enhancements to the antibacterial activity of the AuNP-GCs. To understand the molecular mechanisms of the AuNP-GCs mediated cytotoxicity on the cells and bacteria, in vitro and enzymatical studies were performed. The results showed that the AuNP-GCs selectively alters 6-phosphogluconate accumulation in cancerous and bacterial cells, which could be among the reasons of growth inhibition. Modulations in anti-apoptotic and pro-apoptotic gene expression demonstrated that AuNP-GCs selectively induce apoptosis on cancer cells. Similarly, such sugar ligands and corresponding AuNP-GC selectively inhibited activity of glucosidase. Genetic studies on bacteria (E.coli) showed that AuNP-GCs can strongly alter the synthesis of the genes related to bacterial virulence, stress response, and motility (including flagella and fimbria genes). Therefore, it can be speculated that the current findings can call further research on the development of antibacterial and anticancer chiral gold nanoparticle glycoconjugates.

Chiral gold nanoparticle glycoconjugate synthesis and their anticancer and antibacterial applications relying on carbohydrate-lectin interactions

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.