Abstract
Objective. Layered double hydroxide (LDH) nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML), 5-FU/LDH (FL), and (MTX + 5-FU)/LDH (MFL) nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.
Highlights
Nanotechnology-based drug delivery systems have emerged as powerful methods to enhance drug efficacy and to minimize side effects of cancer chemotherapy [1,2,3,4,5,6]
We have demonstrated the preparation, physicochemical properties, and anticancer efficacy of drug-incorporated layered double hydroxide (LDH) nanohybrids
We adopted reconstruction route to accommodate drug molecules into LDHs preserving topochemical properties of pristine LDHs. Drug molecules such as MTX, 5-FU, and their combination were successfully incorporated to LDH through reconstruction methods preserving the lateral size of LDH nanoparticles
Summary
Nanotechnology-based drug delivery systems have emerged as powerful methods to enhance drug efficacy and to minimize side effects of cancer chemotherapy [1,2,3,4,5,6]. The interlayer anions are stabilized between the LDH layers through electrostatic interaction and safely protected from external harsh conditions [1, 17, 20]. LDHs through various ways: coprecipitation, ion-exchange reaction, reconstruction, and exfoliation-reassembly [21, 22]. Solution containing metal cations and anionic species is titrated with alkaline solution to in situ form anion-incorporated LDH. LDHs are pretreated in mild temperature to produce mixed metal oxide, M(II)1−xM(III)xO(2+x)/2, which recovers layered LDH structure upon addition of water and intended anions. In exfoliation-reassembly route, LDH is treated with an appropriate solvent (usually formamide) to be delaminated into single sheets, which can be restacked to the LDH structure in the presence of anionic species
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