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Posted: Jul 06, 2006

Nanoparticles may play a role in inhibiting the multidrug resistance in chemotherapy

(Nanowerk Spotlight) Multidrug resistance, the principal mechanism by which many cancers develop resistance to chemotherapy drugs, is a major factor in the failure of many forms of chemotherapy. New research by Chinese scientists suggests that nanoparticle surface chemistry and size as well as the unique properties of the magnetic nanoparticles themselves may contribute to a synergistic enhanced effect of drug uptake of targeted cancer cells. These findings could result in promising biomedical applications for cancer therapy.
Professor Xuemei Wang from the the State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory) in Nanjing, PR China, together with several of her colleagues from Southeast University, recently published a paper titled "Synergistic enhancement effect of magnetic nanoparticles on anticancer drug accumulation in cancer cells" in the June 26, 2006 online issue of Nanotechnology.
In it, the researchers describe their investigation of the synergistic effect of three kinds of magnetic nanoparticles, nano Fe3O4, Ni and Fe2O3, on the drug uptake of anticancer drug daunorubicin in leukemia K562 cells.
They show how Fe3O4 nanoparticles could remarkably enhance the uptake or diffusion efficiency of anticancer drugs into target cancer cells (especially drug resistance cancer cells). If Fe3O4 nanoparticles, which are biocompatible and very stable, are fixed at the ailing area by using external magnetic field during the tumor treatment, the chemotherapy effect could be considerably enhanced by combination of the application of the new magnetic nanoparticles in drug delivery systems for achieving the targeting and controlled drug release.
Microscopy images (200 µm 200 µm) of Fe3O4 incubated leukemia cells in the absence and presence of a magnetic field. The cells numbered in the images illustrate the movement of the cells, while squared cells in the left image were observed to move out of vision after the external magnetic field was applied, and the cycled cells in the right image appeared upon application of the external magnetic field. The arrows indicate the direction of the magnetic field and the picture was captured after the magnetic field was applied for 5 s. (Reprinted with permission from IOP Publishing)
"Our results illustrate that the presence of magnetic nanoparticles could facilitate the drug accumulation of daunorubicin inside leukemia cells and the enhancement effect of nano Fe3O4 is much stronger than that of the other two magnetic nanoparticles" Wang explains the findings to Nanowerk. "These observations are consistent with the results of our recent biological experimental studies, which indicates that the presence of Fe3O4 nanoparticles could apparently inhibit the growth of the respective leukemia cells (Interestingly, the Fe3O4 nanoparticle itself could also inhibit the cell growth somehow); especially, when treated the target cells by anticancer drug daunorubicin together with Fe3O4 nanoparticles, the growth of leukemia cells could be much more remarkably inhibited than that with only daunorubicin or other nanoparticles. Since these three kinds of nanoparticles were all capped with the tetraheptylammonium, our observations suggest that both the size and the unique properties of magnetic nanoparticles themselves may contribute to the synergistic enhanced effect of the drug uptake of targeted cancer cells."
The magnetic targeting offers a unique opportunity to treat tumors without systemic toxicity. It is known that the cure efficiency of cancer chemotherapy depends not only on the anticancer drug itself but also on how it is delivered to its targets. As already reported in some literature, it has been observed that the magnetic particles can be targeted and concentrated in some tumor tissue at significantly high level.
"Our observations indicate that magnetic nanoparticles with different size and surface chemistry have different ability to enter target cells and thus the relative efficiency of the drug delivery systems by the conjugation of drugs with nanoparticles will be critically dependent upon nanoparticle surface chemistry and size of the functionalized nanoparticles" says Wang.
"Based on these observations, our future research with regard to cancer therapy may focus on the relative mechanisms of new magnetic nanoparticles" Wang describes a possible direction for her group's future research. "Magnetic nanomaterials are especially promising for the early diagnosis of some cancers and for efficiently targeting chemotherapy.
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