Methotrexate-conjugated quantum dots: synthesis, characterisation and cytotoxicity in drug resistant cancer cells

Abstract

Methotrexate (MTX), a folic acid derivative, is a potent anticancer used for treatment of different malignancies, but possible initiation of drug resistance to MTX by cancer cells has limited its applications. Nanoconjugates (NCs) of MTX to quantum dots (QDs) may favour the cellular uptake via folate receptors (FRs)-mediated endocytosis that circumvents the efflux functions of cancer cells. We synthesised MTX-conjugated l-cysteine capped CdSe QDs (MTX-QD nanoconjugates) and evaluated their internalisation and cytotoxicity in the KB cells with/without resistancy to MTX. The NCs were fully characterised by high resolution transmission electron microscopy (HR-TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and optical spectroscopy. Upon conjugation with MTX, the photoluminescence (PL) properties of QDs altered, while an obvious quenching in PL of QDs was observed after physical mixing. The MTX-QD nanoconjugates efficiently internalised into the cancer cells, and induced markedly high cytotoxicity (IC₅₀, 12.0 µg/mL) in the MTX-resistant KB cells as compared to the free MTX molecules (IC₅₀,105.0 µg/mL), whereas, these values were respectively about 7.0 and 0.6 µg/mL in the MTX-sensitive KB cells. Based on these findings, the MTX-QD nanoconjugates are proposed for the targeted therapy of MTX-resistant cancers, which may provide an improved outcome in the relapsed FR-overexpressing cancers.

• Cancer
• drug delivery
• methotrexate
• nanomedicine
• nanoparticles
• quantum dots
• theranostics

Acknowledgements

We like to thank the Cancer Research Center at Tehran University of Medical Sciences for the technical support. The MTX-resistant KB cells were the courtesy of Dr Najibi (Kharazmi University, Tehran, Iran).

Declaration of interest

The authors declare no conflict of interest. We like to acknowledge the Research Center for Pharmaceutical Nanotechnology (RCPN) at Tabriz University of Medical science (Grant No: 9002, part of a PhD thesis at RCPN) for the financial and technical supports.

Supplementary material available online

Supplementary Figure S1 and Tables S1-S3.