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Lipid-coated gold nanocomposites for enhanced cancer therapy.

Kang JH, Ko YT - Int J Nanomedicine (2015)

Bottom Line: Nanoparticles and their composites were characterized using particle-size analysis, zeta potential measurements, transmission electron microscopy, UV-visible spectroscopy, and reverse-phase high-performance liquid chromatography, demonstrating successful loading of DTX into the lipid bilayer on the surface of the gold nanoparticles.Differential flow cytometry analysis confirmed the improved cellular uptake of lipid-coated nanocomposites.Our preliminary results show that DTX-loaded anionic lipid-coated gold nanorod (AL_AuNR_DTX) and cationic lipid-coated gold nanoparticle (CL_AuNP_DTX) possess effective tumor cell-suppression abilities and can therefore be considered promising chemotherapeutic agents.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Gachon University, Incheon, Republic of Korea.

ABSTRACT
The aim of the work reported here was to develop lipid-coated multifunctional nanocomposites composed of drugs and nanoparticles for use in cancer therapy. We incorporated thermosensitive phospholipids onto the surface of anisotropic gold nanoparticles (AuNPs) to further enhance drug delivery, with possible additional applications for in vivo imaging and photothermal cancer therapy. Lipid-coated nanohybrids loaded with the drug docetaxel (DTX) were prepared by a thin-film formation, hydration, and sonication method. Nanoparticles and their composites were characterized using particle-size analysis, zeta potential measurements, transmission electron microscopy, UV-visible spectroscopy, and reverse-phase high-performance liquid chromatography, demonstrating successful loading of DTX into the lipid bilayer on the surface of the gold nanoparticles. Initial in vitro studies using breast-cancer (MCF-7) and melanoma (B16F10) cell lines demonstrated that the drug-containing nanocomposites at equivalent drug concentrations caused significant cytotoxicity compared to free DTX. Differential flow cytometry analysis confirmed the improved cellular uptake of lipid-coated nanocomposites. Our preliminary results show that DTX-loaded anionic lipid-coated gold nanorod (AL_AuNR_DTX) and cationic lipid-coated gold nanoparticle (CL_AuNP_DTX) possess effective tumor cell-suppression abilities and can therefore be considered promising chemotherapeutic agents. Further evaluation of the therapeutic efficacy of these hybrid nanoparticles combined with external near-infrared photothermal treatment is warranted to assess their synergistic anticancer actions and potential bioimaging applications.

No MeSH data available.


Related in: MedlinePlus

Cell-cycle analysis and the corresponding microscopy images of B16F10 and MCF-7 cells after control treatments and 24-hour incubations with AuNP, CL_AuNP_DTX, AuNR, and AL_AuNR_DTX.Abbreviations: AuNR, gold nanorod; AuNP, spherical gold nanoparticle; AL_AuNR_DTX, docetaxel-loaded anionic lipid-coated gold nanorod; CL_AuNP_DTX, cationic lipid-coated gold nanoparticle; G1, Gap 1; G2/M, Gap 2/Mitosis; S, Synthesis; Sub-G1, Gap 1.
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f8-ijn-10-033: Cell-cycle analysis and the corresponding microscopy images of B16F10 and MCF-7 cells after control treatments and 24-hour incubations with AuNP, CL_AuNP_DTX, AuNR, and AL_AuNR_DTX.Abbreviations: AuNR, gold nanorod; AuNP, spherical gold nanoparticle; AL_AuNR_DTX, docetaxel-loaded anionic lipid-coated gold nanorod; CL_AuNP_DTX, cationic lipid-coated gold nanoparticle; G1, Gap 1; G2/M, Gap 2/Mitosis; S, Synthesis; Sub-G1, Gap 1.

Mentions: B16F10 and MCF-7 cell lines were exposed to CL_NP_DTX and AL_AuNR_DTX and incubated for 24 hours (Figure 8). DTX was found to strongly bind and promote microtubule stabilization, leading to mitotic arrest in the cancer cells. Additionally, DTX induces typical Gap 2 (G2)/Mitosis (M) phase arrest by impairing mitosis and causing chromosomal damage, which corresponds to apoptosis.48,49 As seen in our data, most of the control cells were present in the Gap 1 phase, with limited population in the G2/M phase. The treatment with DTX-loaded nanocomposites, however, resulted in significant G2/M phase arrest in both the cell lines. Initially, only nanoparticle-treated cells showed minimum G2/M phase arrest, with a lower number of apoptotic cells than the control. Interestingly, DTX-loaded formulations elicited a remarkable increase in G2/M phase arrest in both cell lines. B16F10 cells, in particular, elicited a remarkable increase in G2/M phase arrest, corresponding to a significant apoptotic cell population, which indicates the synergistic cytotoxic action of DTX. The corresponding microscopy images may explain the fate of cells after treatment. In B16F10 cells, the CL_NP_DTX formulation showed a high level of cell death as evidenced by reduced cell numbers, whereas, in MCF-7 cells, the formulation caused more round floating cells, which might due to cell-cycle arrest leading to apoptosis. The enhanced cell-cycle arrest followed by apoptosis observed with the CL_NP_DTX formulation may reflect DTX toxicity. The G2/M phase arrest in MCF-7 cell line could be expected to enhance apoptosis with a prolonged incubation time beyond 24 hours.


Lipid-coated gold nanocomposites for enhanced cancer therapy.

Kang JH, Ko YT - Int J Nanomedicine (2015)

Cell-cycle analysis and the corresponding microscopy images of B16F10 and MCF-7 cells after control treatments and 24-hour incubations with AuNP, CL_AuNP_DTX, AuNR, and AL_AuNR_DTX.Abbreviations: AuNR, gold nanorod; AuNP, spherical gold nanoparticle; AL_AuNR_DTX, docetaxel-loaded anionic lipid-coated gold nanorod; CL_AuNP_DTX, cationic lipid-coated gold nanoparticle; G1, Gap 1; G2/M, Gap 2/Mitosis; S, Synthesis; Sub-G1, Gap 1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554419&req=5

f8-ijn-10-033: Cell-cycle analysis and the corresponding microscopy images of B16F10 and MCF-7 cells after control treatments and 24-hour incubations with AuNP, CL_AuNP_DTX, AuNR, and AL_AuNR_DTX.Abbreviations: AuNR, gold nanorod; AuNP, spherical gold nanoparticle; AL_AuNR_DTX, docetaxel-loaded anionic lipid-coated gold nanorod; CL_AuNP_DTX, cationic lipid-coated gold nanoparticle; G1, Gap 1; G2/M, Gap 2/Mitosis; S, Synthesis; Sub-G1, Gap 1.
Mentions: B16F10 and MCF-7 cell lines were exposed to CL_NP_DTX and AL_AuNR_DTX and incubated for 24 hours (Figure 8). DTX was found to strongly bind and promote microtubule stabilization, leading to mitotic arrest in the cancer cells. Additionally, DTX induces typical Gap 2 (G2)/Mitosis (M) phase arrest by impairing mitosis and causing chromosomal damage, which corresponds to apoptosis.48,49 As seen in our data, most of the control cells were present in the Gap 1 phase, with limited population in the G2/M phase. The treatment with DTX-loaded nanocomposites, however, resulted in significant G2/M phase arrest in both the cell lines. Initially, only nanoparticle-treated cells showed minimum G2/M phase arrest, with a lower number of apoptotic cells than the control. Interestingly, DTX-loaded formulations elicited a remarkable increase in G2/M phase arrest in both cell lines. B16F10 cells, in particular, elicited a remarkable increase in G2/M phase arrest, corresponding to a significant apoptotic cell population, which indicates the synergistic cytotoxic action of DTX. The corresponding microscopy images may explain the fate of cells after treatment. In B16F10 cells, the CL_NP_DTX formulation showed a high level of cell death as evidenced by reduced cell numbers, whereas, in MCF-7 cells, the formulation caused more round floating cells, which might due to cell-cycle arrest leading to apoptosis. The enhanced cell-cycle arrest followed by apoptosis observed with the CL_NP_DTX formulation may reflect DTX toxicity. The G2/M phase arrest in MCF-7 cell line could be expected to enhance apoptosis with a prolonged incubation time beyond 24 hours.

Bottom Line: Nanoparticles and their composites were characterized using particle-size analysis, zeta potential measurements, transmission electron microscopy, UV-visible spectroscopy, and reverse-phase high-performance liquid chromatography, demonstrating successful loading of DTX into the lipid bilayer on the surface of the gold nanoparticles.Differential flow cytometry analysis confirmed the improved cellular uptake of lipid-coated nanocomposites.Our preliminary results show that DTX-loaded anionic lipid-coated gold nanorod (AL_AuNR_DTX) and cationic lipid-coated gold nanoparticle (CL_AuNP_DTX) possess effective tumor cell-suppression abilities and can therefore be considered promising chemotherapeutic agents.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Gachon University, Incheon, Republic of Korea.

ABSTRACT
The aim of the work reported here was to develop lipid-coated multifunctional nanocomposites composed of drugs and nanoparticles for use in cancer therapy. We incorporated thermosensitive phospholipids onto the surface of anisotropic gold nanoparticles (AuNPs) to further enhance drug delivery, with possible additional applications for in vivo imaging and photothermal cancer therapy. Lipid-coated nanohybrids loaded with the drug docetaxel (DTX) were prepared by a thin-film formation, hydration, and sonication method. Nanoparticles and their composites were characterized using particle-size analysis, zeta potential measurements, transmission electron microscopy, UV-visible spectroscopy, and reverse-phase high-performance liquid chromatography, demonstrating successful loading of DTX into the lipid bilayer on the surface of the gold nanoparticles. Initial in vitro studies using breast-cancer (MCF-7) and melanoma (B16F10) cell lines demonstrated that the drug-containing nanocomposites at equivalent drug concentrations caused significant cytotoxicity compared to free DTX. Differential flow cytometry analysis confirmed the improved cellular uptake of lipid-coated nanocomposites. Our preliminary results show that DTX-loaded anionic lipid-coated gold nanorod (AL_AuNR_DTX) and cationic lipid-coated gold nanoparticle (CL_AuNP_DTX) possess effective tumor cell-suppression abilities and can therefore be considered promising chemotherapeutic agents. Further evaluation of the therapeutic efficacy of these hybrid nanoparticles combined with external near-infrared photothermal treatment is warranted to assess their synergistic anticancer actions and potential bioimaging applications.

No MeSH data available.


Related in: MedlinePlus