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Anticancer drug-incorporated layered double hydroxide nanohybrids and their enhanced anticancer therapeutic efficacy in combination cancer treatment.

Kim TH, Lee GJ, Kang JH, Kim HJ, Kim TI, Oh JM - Biomed Res Int (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry & Medical Chemistry, College of Science & Technology, Yonsei University, Wonju, Gangwon-do 220-710, Republic of Korea.

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.

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Related in: MedlinePlus

(a) The surface charge (ζ-potential) distribution graph of ML in deionized water (—■—) at pH 8.3 (average ζ-potential: −0.61 mV), DMEM (—●—) at pH 7.88 (average ζ-potential: −8.94 mV), and DMEM with 10% FBS (—▲—) at pH 7.86 (average ζ-potential: 12.47 mV). (b) The surface charge (ζ-potential) distribution graph of FL in deionized water (—■—) at pH 8.35 (average ζ-potential: 36.99 mV), DMEM (—●—) at pH 7.95 (average ζ-potential: −17.07 mV), and DMEM with 10% FBS (—▲—) at pH 8.02 (average ζ-potential: 12.19 mV). (c) The surface charge (ζ-potential) distribution graph of MFL in deionized water (—■—) at pH 8.47 (average ζ-potential: −2.08 mV), DMEM (—●—) at pH 8.02 (average ζ-potential: −15.96 mV), and DMEM with 10% FBS (—▲—) at pH 8.03 (average ζ-potential: 7.64 mV). The vertical line stands for the zeta potential value of 0 mV.
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fig4: (a) The surface charge (ζ-potential) distribution graph of ML in deionized water (—■—) at pH 8.3 (average ζ-potential: −0.61 mV), DMEM (—●—) at pH 7.88 (average ζ-potential: −8.94 mV), and DMEM with 10% FBS (—▲—) at pH 7.86 (average ζ-potential: 12.47 mV). (b) The surface charge (ζ-potential) distribution graph of FL in deionized water (—■—) at pH 8.35 (average ζ-potential: 36.99 mV), DMEM (—●—) at pH 7.95 (average ζ-potential: −17.07 mV), and DMEM with 10% FBS (—▲—) at pH 8.02 (average ζ-potential: 12.19 mV). (c) The surface charge (ζ-potential) distribution graph of MFL in deionized water (—■—) at pH 8.47 (average ζ-potential: −2.08 mV), DMEM (—●—) at pH 8.02 (average ζ-potential: −15.96 mV), and DMEM with 10% FBS (—▲—) at pH 8.03 (average ζ-potential: 7.64 mV). The vertical line stands for the zeta potential value of 0 mV.

Mentions: Most of the nanodrug delivery systems for cellular delivery are administered in aqueous suspension or solution state. Thus it is essential to investigate their physicochemical properties in suspension, such as zeta potential and hydrodynamic size. Especially, zeta potential which reflects the surface charge is considered as an important factor to decide interaction between nanomaterials and cells [44–46]. Usually plasma membranes of mammalian cells are negatively charged due to the phospholipid bilayers and carbohydrates embedded in the membrane [47, 48]. Many reports highlighted that the positively charged nanomaterials interact more actively with cell membranes [49–53], eventually resulting in the enhanced cellular uptake. LDHs are usually known to have positive layer charge; however, the surface charge of LDH can be affected by both the surface coated molecules and the type or concentration of electrolytes or solutes in the suspending media [54]. Therefore, we carried out zeta potential measurement in three different media including deionized water and cell culture medium (DMEM) with or without FBS. The zeta potential values of three nanohybrids in deionized water were −0.61, +36.9, and −2.08 mV for ML, FL, and MFL, respectively. According to the zeta potential distribution graph, more than half of the zeta potential values lie in the positive region (Figure 4). Nanohybrids having MTX moiety (ML and MFL) showed relatively negative surface charge compared with FL. As MTX had two anionic carboxylate groups and some of the MTX molecules are attached on the outer surface of LDH, it was thought that the surface charge of those nanohybrids (ML and MFL) showed negative values.


Anticancer drug-incorporated layered double hydroxide nanohybrids and their enhanced anticancer therapeutic efficacy in combination cancer treatment.

Kim TH, Lee GJ, Kang JH, Kim HJ, Kim TI, Oh JM - Biomed Res Int (2014)

(a) The surface charge (ζ-potential) distribution graph of ML in deionized water (—■—) at pH 8.3 (average ζ-potential: −0.61 mV), DMEM (—●—) at pH 7.88 (average ζ-potential: −8.94 mV), and DMEM with 10% FBS (—▲—) at pH 7.86 (average ζ-potential: 12.47 mV). (b) The surface charge (ζ-potential) distribution graph of FL in deionized water (—■—) at pH 8.35 (average ζ-potential: 36.99 mV), DMEM (—●—) at pH 7.95 (average ζ-potential: −17.07 mV), and DMEM with 10% FBS (—▲—) at pH 8.02 (average ζ-potential: 12.19 mV). (c) The surface charge (ζ-potential) distribution graph of MFL in deionized water (—■—) at pH 8.47 (average ζ-potential: −2.08 mV), DMEM (—●—) at pH 8.02 (average ζ-potential: −15.96 mV), and DMEM with 10% FBS (—▲—) at pH 8.03 (average ζ-potential: 7.64 mV). The vertical line stands for the zeta potential value of 0 mV.
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Related In: Results  -  Collection

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fig4: (a) The surface charge (ζ-potential) distribution graph of ML in deionized water (—■—) at pH 8.3 (average ζ-potential: −0.61 mV), DMEM (—●—) at pH 7.88 (average ζ-potential: −8.94 mV), and DMEM with 10% FBS (—▲—) at pH 7.86 (average ζ-potential: 12.47 mV). (b) The surface charge (ζ-potential) distribution graph of FL in deionized water (—■—) at pH 8.35 (average ζ-potential: 36.99 mV), DMEM (—●—) at pH 7.95 (average ζ-potential: −17.07 mV), and DMEM with 10% FBS (—▲—) at pH 8.02 (average ζ-potential: 12.19 mV). (c) The surface charge (ζ-potential) distribution graph of MFL in deionized water (—■—) at pH 8.47 (average ζ-potential: −2.08 mV), DMEM (—●—) at pH 8.02 (average ζ-potential: −15.96 mV), and DMEM with 10% FBS (—▲—) at pH 8.03 (average ζ-potential: 7.64 mV). The vertical line stands for the zeta potential value of 0 mV.
Mentions: Most of the nanodrug delivery systems for cellular delivery are administered in aqueous suspension or solution state. Thus it is essential to investigate their physicochemical properties in suspension, such as zeta potential and hydrodynamic size. Especially, zeta potential which reflects the surface charge is considered as an important factor to decide interaction between nanomaterials and cells [44–46]. Usually plasma membranes of mammalian cells are negatively charged due to the phospholipid bilayers and carbohydrates embedded in the membrane [47, 48]. Many reports highlighted that the positively charged nanomaterials interact more actively with cell membranes [49–53], eventually resulting in the enhanced cellular uptake. LDHs are usually known to have positive layer charge; however, the surface charge of LDH can be affected by both the surface coated molecules and the type or concentration of electrolytes or solutes in the suspending media [54]. Therefore, we carried out zeta potential measurement in three different media including deionized water and cell culture medium (DMEM) with or without FBS. The zeta potential values of three nanohybrids in deionized water were −0.61, +36.9, and −2.08 mV for ML, FL, and MFL, respectively. According to the zeta potential distribution graph, more than half of the zeta potential values lie in the positive region (Figure 4). Nanohybrids having MTX moiety (ML and MFL) showed relatively negative surface charge compared with FL. As MTX had two anionic carboxylate groups and some of the MTX molecules are attached on the outer surface of LDH, it was thought that the surface charge of those nanohybrids (ML and MFL) showed negative values.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry & Medical Chemistry, College of Science & Technology, Yonsei University, Wonju, Gangwon-do 220-710, Republic of Korea.

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.

Show MeSH
Related in: MedlinePlus