Thiol functionalised gold nanoparticles loaded with methotrexate for cancer treatment: From synthesis to in vitro studies on neuroblastoma cell lines

Hypothesis: Colloidal gold nanoparticles (AuNPs) functionalised with hydrophilic thiols can be used as drug delivery probes, thanks to their small size and hydrophilic character. AuNPs possess unique properties for their use in nanomedicine, especially in cancer treatment, as diagnostics and therapeutic tools. Experiments: Thiol functionalised AuNPs were synthesised and loaded with methotrexate (MTX). Spectroscopic and morphostructural characterisations evidenced the stability of the colloids upon interaction with MTX. Solid state (GISAXS, GIWAXS, FESEM, TEM, FTIR-ATR, XPS) and dispersed phase (UV-Vis, DLS, & zeta;-potential, NMR, SAXS) experiments allowed to understand structure-properties correlations. The nanoconjugate was tested in vitro (MTT assays) against two neuroblastoma cell lines: SNJKP and IMR5 with overexpressed n-Myc. Findings: Molar drug encapsulation efficiency was optimised to be >70%. A non-covalent interaction between the & pi; system and the carboxylate moiety belonging to MTX and the charged aminic group of one of the thiols was found. The MTX loading slightly decreased the structural order of the system and increased the distance between the AuNPs. Free AuNPs showed no cytotoxicity whereas the AuNPs-MTX nanoconjugate had a more potent effect when compared to free MTX. The active role of AuNPs was evidenced by permeation studies: an improvement on penetration of the drug inside cells was evidenced.

Automated summary

This study demonstrates that hydrophilic thiol-functionalized colloidal gold nanoparticles (AuNPs) can be used as drug delivery probes due to their small size and hydrophilic nature. AuNPs possess unique properties for their applications in nanomedicine, especially in cancer treatment as diagnostics and therapeutic tools. The experiments conducted included spectroscopic and morphostructural characterizations, as well as solid state and dispersed phase experiments, aiming to understand the structure-properties correlations. In vitro studies showed that the MTX-loaded AuNPs had a more potent effect compared to free MTX, and the active role of AuNPs in drug penetration was evidenced.