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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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Scanning electron microscopic images of (a) MgAl-LDH, (b) mixed metal oxide, and drug/LDH nanohybrids: (c) ML, (d) FL, and (e) MFL.
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fig1: Scanning electron microscopic images of (a) MgAl-LDH, (b) mixed metal oxide, and drug/LDH nanohybrids: (c) ML, (d) FL, and (e) MFL.

Mentions: Size and morphology of pristine Mg2Al(OH)6(CO3)0.5-LDH, calcined LDH, and drug/LDH nanohybrids were visualized with SEM as displayed in Figure 1. The particle size distribution of each sample was highly homogenous and the morphology showed characteristic feature of LDHs and organic-incorporated LDHs as reported previously [38, 39]. The lateral particle size and thickness of pristine LDH were ~233 ± 12 and ~100 ± 16 nm, respectively. Those values for calcined LDHs were determined to be ~236 ± 13 and ~73 ± 11 nm, respectively. From Student's t-test with 95% confidentiality, it was confirmed that the lateral particle size of LDH preserved after calcinations while the particle thickness reduced significantly. It has been reported that the LDH layers topochemically underwent dehydration, dehydroxylation, and decarbonation during heat treatment [40]. Therefore, the xy-plane was not altered much and the interlayer distance reduced significantly with the removal of interlayer carbonate. The morphology of drug/LDH nanohybrids was fairly different from that of LDH or calcined one, showing rosette-like shape with very much reduced particle thickness, less than 20 nm, and bending of layers. Decrease in thickness was attributed to the partial delamination of LDHs during intercalation of drug molecules like MTX or 5-FU. The rosette-like structure or house-of-cards structure, which is due to the enhanced particle-edge interaction, has been reported as a typical feature of organic/LDH hybrids obtained by reconstruction route [39, 41]. Although it was difficult to estimate the lateral particle size of drug/LDH nanohybrids due to the randomly stacked thin and bended layers, we found that the lateral sizes of drug/LDH nanohybrids were ~225 ± 14, ~236 ± 12, and ~234 ± 14 nm for ML, FL, and MFL, respectively, from repeated SEM measurements (see Figure S1 in Supplementary Material available online at http://dx.doi.org/10.1155/2014/193401). From the results that the lateral particle sizes were preserved during reconstruction synthesis and only thickness slightly changed, we could suggest reconstruction as an appropriate way to topochemically incorporate drug molecules into LDHs preserving the 2-dimensional structure of LDH nanocarrier.


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)

Scanning electron microscopic images of (a) MgAl-LDH, (b) mixed metal oxide, and drug/LDH nanohybrids: (c) ML, (d) FL, and (e) MFL.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016841&req=5

fig1: Scanning electron microscopic images of (a) MgAl-LDH, (b) mixed metal oxide, and drug/LDH nanohybrids: (c) ML, (d) FL, and (e) MFL.
Mentions: Size and morphology of pristine Mg2Al(OH)6(CO3)0.5-LDH, calcined LDH, and drug/LDH nanohybrids were visualized with SEM as displayed in Figure 1. The particle size distribution of each sample was highly homogenous and the morphology showed characteristic feature of LDHs and organic-incorporated LDHs as reported previously [38, 39]. The lateral particle size and thickness of pristine LDH were ~233 ± 12 and ~100 ± 16 nm, respectively. Those values for calcined LDHs were determined to be ~236 ± 13 and ~73 ± 11 nm, respectively. From Student's t-test with 95% confidentiality, it was confirmed that the lateral particle size of LDH preserved after calcinations while the particle thickness reduced significantly. It has been reported that the LDH layers topochemically underwent dehydration, dehydroxylation, and decarbonation during heat treatment [40]. Therefore, the xy-plane was not altered much and the interlayer distance reduced significantly with the removal of interlayer carbonate. The morphology of drug/LDH nanohybrids was fairly different from that of LDH or calcined one, showing rosette-like shape with very much reduced particle thickness, less than 20 nm, and bending of layers. Decrease in thickness was attributed to the partial delamination of LDHs during intercalation of drug molecules like MTX or 5-FU. The rosette-like structure or house-of-cards structure, which is due to the enhanced particle-edge interaction, has been reported as a typical feature of organic/LDH hybrids obtained by reconstruction route [39, 41]. Although it was difficult to estimate the lateral particle size of drug/LDH nanohybrids due to the randomly stacked thin and bended layers, we found that the lateral sizes of drug/LDH nanohybrids were ~225 ± 14, ~236 ± 12, and ~234 ± 14 nm for ML, FL, and MFL, respectively, from repeated SEM measurements (see Figure S1 in Supplementary Material available online at http://dx.doi.org/10.1155/2014/193401). From the results that the lateral particle sizes were preserved during reconstruction synthesis and only thickness slightly changed, we could suggest reconstruction as an appropriate way to topochemically incorporate drug molecules into LDHs preserving the 2-dimensional structure of LDH nanocarrier.

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