Scientists under Dr. Youqing Shen at the University of Wyoming have developed nanoparticles designed to target cell nucleus and capable of carrying medications. The research might eventually have implications for gene therapy, targeted chemotherapy, etc.
Michael Berger at Nanowerk reports:
Shen is an Associate Professor of Chemical and Petroleum Engineering at the University of Wyoming. Together with colleagues from the university he developed a novel approach to fabricating nuclear localization nanoparticles. The key to their technique is a pH-triggered charge reversal.
“We have demonstrated nanoparticles with a negative-to-positive charge-reversal outer layer (made of polyethyleneimine, or PEI) triggered by the solid tumor extracellular or the lysosomal acidity for nuclear drug delivery” says Shen.
PEI is widely used in gene delivery and it was found that it can localize in the nucleus. The scientists hypothesized that nanoparticles functionalized with PEI may also be able to localize into the nucleus. “However” says Shen, “positively charged particles or polymers cannot be directly used in the body because the body’s immune system would clear them out from the bloodstream very quickly. Our charge-reversal technique makes it possible for the PEI-functionalized nanoparticles to be used in the body: They are negatively charged and thus do not interact with the blood components. But once in the solid tumor or tumor cells they regenerate as PEI-functionalized nanoparticles for nuclear localization.”
Naming them “targeted charge-reversal nanoparticles” (TCRNs), the researchers loaded their nanoparticles with doxorubicin (DOX), an anticancer drug used in chemotherapy. In their experiments they found that the percentage of DOX-positive cells cultured with TCRNs/DOX was significantly higher than that cultured with free DOX under the same conditions at pH 7.4 (the average body pH).
“Our findings suggest that the TCRNs could efficiently cross the cell membrane, escape from the lysosomes, and localize and deliver DOX in the nucleus to result in a greater cytotoxicity” says Shen. “This is the first type of nanoparticles capable of localizing into the nucleus. This type of nanoparticles and the charge-reversal techniques will also be useful in gene delivery.”
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