BACKGROUNDThe development of drug resistant Mycobacterium strains is a serious health concern causing impairment in tuberculosis (TB) therapy. UsingMycobacteriumsmegmatis as a model, the possible enhancement in the efficacy of first-line anti-TB drugs, isoniazid and rifampicin, is explored by using a combined strategy of treating the cells simultaneously with both drug and nanoparticles. The latter can target the tough cell wall of mycobacteria. RESULTSBiocompatible citric acid-coated iron oxide (magnetite) nanoparticles (CA-MNP) were synthesized by a co-precipitation routewith an average diameter of 9nm. The uptake of nanoparticles byM. smegmatiswas proportional to its concentration up to 32 mu g mL(-1). Real-time studies on fluorescent tracers demonstrate that the nanoparticles enhance membrane permeability, aiding in a higher influx of drugs into the cells. Intracellular rifampicin levels were enhanced 2-fold in the presence of CA-MNP, compared with that in the absence of CA-MNP. Similarly, reactive oxygen species (ROS) levels, measured as an indication of intracellular isoniazid, increased in cells treated with both nanoparticles and isoniazid, compared with when only the drug was used. CONCLUSIONCA-MNP in conjunction with either isoniazid or rifampicin displayed a synergistic effect in inhibiting bacterial growth, leading to a 2-fold reduction in the drug dosage. This study demonstrates that the enhanced uptake of existing anti-Tb drugs using nanoparticles is a possible option in tuberculosis treatment. (c) 2015 Society of Chemical Industry