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Novel Strategy to Fabricate PLA/Au Nanocomposites as an Efficient Drug Carrier for Human Leukemia Cells in Vitro

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ABSTRACT

Poly (lactic acid) (PLA) polymer has the promising applications in the biomedical field because of its biodegradability and safe elimination. In this study, we have explored the bio-application of new nanocomposites composed with PLA nanofibers and Au nanoparticles as the potential drug carrier for an efficient drug delivery in target cancer cells. The results demonstrated that the anticancer drug daunorubicin could be efficiently self-assembled on the surface of PLA/Au nanocomposites and the synergistic enhancement of PLA/Au nanocomposites conjugated with daunorubicin into drug-sensitive K562 and drug-resistant leukemia K562/AO2 cells could be obviously observed by MTT assay and confocal fluorescence microscopy studies. These observations suggest that the new nanocomposites could readily induce daunorubicin to accumulate and uptake in target leukemia cells and increase the drug's cytotoxicity. Especially, the PLA/Au nanocomposites could significantly facilitate the cellular drug absorbtion of daunorubicin into drug-resistant K562/AO2 cells and efficiently inhibit the cancer cell proliferation. This raised the possibility to utilize the PLA/Au nanocomposites as a new effective additive agent to inhibit the drug resistance and thus as a novel strategy to sensitively track the respective cancer cells.

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MTT assay to test the cytotoxicity of DNR in the presence of PLA or PLA/Au nanocomposites for K562 cells (a) and K562/AO2 cells (b) for 48 h. Error bars, ±SEM.
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Figure 5: MTT assay to test the cytotoxicity of DNR in the presence of PLA or PLA/Au nanocomposites for K562 cells (a) and K562/AO2 cells (b) for 48 h. Error bars, ±SEM.

Mentions: The cell viability of leukemia cancer cells in the presence of PLA/Au nanocomposites loaded with DNR has been explored by MTT assay. As shown in Figure 5, the results demonstrate that the combination of the PLA/Au nanocomposites with DNR could more effectively inhibit the growth of these two different kinds of leukemia cells than that treated with DNR alone. It is evident that the biocompatible PLA/Au nanocomposites have a synergistic effect to facilitate the drug uptake into human leukemia cells, increase the relative intracellular drug concentration and hence enhance the cytotoxicity of anticancer agents. Meanwhile, it is observed that the inhibition effect for drug-resistant K562/AO2 cancer cells was relatively significant than that for drug-sensitive K562 cancer cells when treated with DNR conjugated with PLA/Au nanocomposites. As shown in Table 1, our results revealed that the resistant factor of the reversal index to resistant leukemia cells was 70.14 for K562/A02 in the control group, while the resistant factor in the presence of the PLA/Au nanocomposites significantly decreased to 38.88; therefore, the reversal index to K562/A02 was 1.8. This suggests that the presence of PLA/Au nanocomposites can reinforce the accumulation of DNR in drug-resistant K562/A02 cells and lead to a great extent decreasing of the resisting factors. Thus, the interaction of PLA/Au nanocomposites with bioactive molecules on the cell membrane could provide a new strategy to overcome the multidrug resistance (MDR) of K562/AO2 cells by improving the efficiency of drug delivery. These observations were coherent with the above results of confocal fluorescence studies.


Novel Strategy to Fabricate PLA/Au Nanocomposites as an Efficient Drug Carrier for Human Leukemia Cells in Vitro
MTT assay to test the cytotoxicity of DNR in the presence of PLA or PLA/Au nanocomposites for K562 cells (a) and K562/AO2 cells (b) for 48 h. Error bars, ±SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3211355&req=5

Figure 5: MTT assay to test the cytotoxicity of DNR in the presence of PLA or PLA/Au nanocomposites for K562 cells (a) and K562/AO2 cells (b) for 48 h. Error bars, ±SEM.
Mentions: The cell viability of leukemia cancer cells in the presence of PLA/Au nanocomposites loaded with DNR has been explored by MTT assay. As shown in Figure 5, the results demonstrate that the combination of the PLA/Au nanocomposites with DNR could more effectively inhibit the growth of these two different kinds of leukemia cells than that treated with DNR alone. It is evident that the biocompatible PLA/Au nanocomposites have a synergistic effect to facilitate the drug uptake into human leukemia cells, increase the relative intracellular drug concentration and hence enhance the cytotoxicity of anticancer agents. Meanwhile, it is observed that the inhibition effect for drug-resistant K562/AO2 cancer cells was relatively significant than that for drug-sensitive K562 cancer cells when treated with DNR conjugated with PLA/Au nanocomposites. As shown in Table 1, our results revealed that the resistant factor of the reversal index to resistant leukemia cells was 70.14 for K562/A02 in the control group, while the resistant factor in the presence of the PLA/Au nanocomposites significantly decreased to 38.88; therefore, the reversal index to K562/A02 was 1.8. This suggests that the presence of PLA/Au nanocomposites can reinforce the accumulation of DNR in drug-resistant K562/A02 cells and lead to a great extent decreasing of the resisting factors. Thus, the interaction of PLA/Au nanocomposites with bioactive molecules on the cell membrane could provide a new strategy to overcome the multidrug resistance (MDR) of K562/AO2 cells by improving the efficiency of drug delivery. These observations were coherent with the above results of confocal fluorescence studies.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Poly (lactic acid) (PLA) polymer has the promising applications in the biomedical field because of its biodegradability and safe elimination. In this study, we have explored the bio-application of new nanocomposites composed with PLA nanofibers and Au nanoparticles as the potential drug carrier for an efficient drug delivery in target cancer cells. The results demonstrated that the anticancer drug daunorubicin could be efficiently self-assembled on the surface of PLA/Au nanocomposites and the synergistic enhancement of PLA/Au nanocomposites conjugated with daunorubicin into drug-sensitive K562 and drug-resistant leukemia K562/AO2 cells could be obviously observed by MTT assay and confocal fluorescence microscopy studies. These observations suggest that the new nanocomposites could readily induce daunorubicin to accumulate and uptake in target leukemia cells and increase the drug's cytotoxicity. Especially, the PLA/Au nanocomposites could significantly facilitate the cellular drug absorbtion of daunorubicin into drug-resistant K562/AO2 cells and efficiently inhibit the cancer cell proliferation. This raised the possibility to utilize the PLA/Au nanocomposites as a new effective additive agent to inhibit the drug resistance and thus as a novel strategy to sensitively track the respective cancer cells.

No MeSH data available.


Related in: MedlinePlus