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Nanotech News


February 5, 2007

Heat and pH-Sensitive Nanoparticles Designed to Target Tumors

Using a novel polymer that becomes unstable under the pH conditions inside tumor cells, investigators at Singapore’s Institute of Bioengineering and Nanotechnology have developed a core-shell nanoparticle targeted to deliver drugs to tumors. Because of the design of the polymer, the nanoparticles assemble on their own when mixed with water-insoluble anticancer agents, including doxorubicin and paclitaxel.

Reporting its work in two papers – the first appears in the journal Biomaterials, the second in the journal Advanced Functional Materials – the research group headed by Yi Yan Yang, Ph.D., first developed a biocompatible polymer that forms nanoparticles that are stable at the pH found outside of cells but that become unstable in the acidic environment inside tumor cells. When the nanoparticles become unstable, they release drug molecules sequestered in their hydrophobic, or water-avoiding, cores. The hydrophobic core of this nanoparticle provides an accommodating environment for water-insoluble drugs such as doxorubicin and paclitaxel.

To target tumor cells, the investigators developed a method for chemically attaching folic acid to the exterior shell of these nanoparticles. Folic acid binds to a receptor that is overexpressed on the surfaces of many types of tumor cells. Tests with folic acid-labeled nanoparticles containing either doxorubicin or paclitaxel showed that these nanoparticles are taken up rapidly by targeted tumor cells but not by healthy cells or tumor cells that do not bear the folic acid receptor. These targeting experiments also demonstrated that increased uptake of the drug-laden nanoparticles translated into increased potency for the delivered drugs.

The work with doxorubicin-loaded nanoparticles is detailed in a paper titled, “Multifunctional core/shell nanoparticles self-assembled from pH-induced thermosensitive polymers for targeted intracellular anticancer drug delivery.” This work was published online in advance of print publication. An abstract of this paper is available at the journal’s website.
View abstract.

The work with paclitaxel-loaded nanoparticles is detailed in a paper titled, “Targeted and intracellular delivery of paclitaxel using multi-functional polymeric micelles.” This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.
View abstract.