title: 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.
authors.affiliation: a Research Centre for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran .|b School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences , Tabriz , Iran , and.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Johari-Ahar
authors.affiliation: a Research Centre for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran .|b School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences , Tabriz , Iran , and.
authors.forename: Jaleh
authors.initials: J
authors.lastname: Barar
authors.affiliation: c Cancer Research Centre, Tehran University of Medical Sciences , Tehran , Iran.
authors.forename: Ali Mohammad
authors.initials: AM
authors.lastname: Alizadeh
authors.affiliation: a Research Centre for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran .|b School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences , Tabriz , Iran , and.
authors.forename: Soodabeh
authors.initials: S
authors.lastname: Davaran
authors.affiliation: a Research Centre for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran .|b School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences , Tabriz , Iran , and.
authors.forename: Yadollah
authors.initials: Y
authors.lastname: Omidi
authors.affiliation: a Research Centre for Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences , Tabriz , Iran .|b School of Advanced Biomedical Sciences, Tabriz University of Medical Sciences , Tabriz , Iran , and.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Rashidi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003545:Cysteine / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004705:Endocytosis / Q000187:drug effects; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D007624:KB Cells; D008727:Methotrexate / Q000008:administration & dosage* / Q000737:chemistry*; D058726:Nanoconjugates / Q000008:administration & dosage* / Q000737:chemistry*; D045663:Quantum Dots / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D058726:Nanoconjugates; D005492:Folic Acid; D003545:Cysteine; D008727:Methotrexate
keywords: Cancer; drug delivery; methotrexate; nanomedicine; nanoparticles; quantum dots; theranostics