Mg-Al layered double hydroxide nanoparticles were synthesized by one-pot co-precipitation method and anticancerous drug methotrexate was incorporated into it by in-situ ion exchange. The LDH-MTX nanohybrid produced moderately stable suspension in water, as predicted by zeta potential measurement. X-ray diffraction revealed that the basal spacing increased to nearly twice the same for pristine LDH on MTX intercalation. Thermogravimetric analyses confirmed an increase in thermal stability of the intercalated drug in the LDH framework. A striking enhancement in efficacy/sensitivity of MTX on the HCT-116 cells was obtained when intercalated within the LDH layers, as revealed by the attainment of half maximal inhibitory concentration of LDH-MTX nanohybrid by 48 h, whereas, bare MTX required 72 h for the same. The MTX release from MgAl-LDH-MTX hybrids in phosphate buffer saline at pH 7.4 followed a relatively slow, first order kinetics and was complete within 8 days following diffusion and crystal dissolution mechanism. (C) 2013 Elsevier B.V. All rights reserved