Synthesis of methotrexate-conjugated gold nanoparticles with enhanced cancer therapeutic effect

• We synthesized methotrexate-Au NP conjugate as anticancer drug release system.
• Methotrexate acts as both a reducing agent and a capping molecule.
• MTT and LDH tests showed conjugates exhibit high cytotoxic effects on cancer cells.

We have developed a simple approach to synthesize gold nanoparticle (AuNP) by utilizing the anti-cancer drug, methotrexate (MTX), as both the reducing agent and the capping molecule. MTX-conjugated AuNPs (MTX-AuNPs) of various sizes (∼3 and ∼20 nm) can be obtained in a one-pot synthesis. We utilized transmission electron microscopy, X-ray diffraction, and UV–vis spectroscopy to characterize these nanoparticles, and Fourier-transform infrared (FTIR) spectroscopy and Raman spectroscopy to investigate the chemical interactions between the MTX and AuNPs. To examine the cancer therapeutic effect of these nanoparticles, we applied the lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay tests. The results demonstrated that the MTX-AuNPs of small size (∼3 nm) exhibited considerably high cytotoxic effects in human choriocarcinoma cell lines compared to the effects of equal doses of free MTX; these results suggest that anti-cancer drug-conjugated AuNPs have an enhanced therapeutic effect.