Nanotech News

August 22, 2005

Targeted pH Sensitive Nanoparticle Releases Drug Inside Tumor Cells

A multidisciplinary team of investigators at the University of Tokyo in Japan has created a self-assembling nanostructure that targets human cancer cells and releases drug molecules in response to a change in pH that is characteristic of many types of cancer (click here for more on self-assembly). This work was published in the journal Molecular BioSystems.

Kazunori Kataoka, Ph.D., led the team that developed the novel polymer that self-assembles into pH-sensitive nanoparticles. Each chain of this polymer contains folic acid at one end followed by alternating blocks of a hydrophobic (water-avoiding) and hydrophilic (water-seeking) polymer in between. The anticancer drug adriamycin is attached to the hydrophobic segments via an acid-sensitive linker. In water, polymer chains come together, or self-assemble, to form a hydrophobic core containing adriamycin and a hydrophilic surface decorated with the targeting agent folic acid. Once these particles are taken up by cancer cells, thanks to the interaction between the folic acid molecules on the surface of the nanoparticle and a folate receptor on the surface of cancer cells, the acidic pH inside the cell causes the particles to release their drug payload.

Studies with cultured folate-responsive cancer cells showed that the targeted nanoparticles were capable of achieving higher intracellular drug levels than when free adriamycin was administered to these cells. More importantly, the nanoparticulate formulation was more effective at killing cells than was free adriamycin.

This work is detailed in a paper titled, “Multifunctional polymeric micelles with folate-mediated cancer cell targeting and pH-triggered drug releasing properties for active intracellular drug delivery.” This article was posted online in advance of print publication. The full-text paper is available free-of-charge through the journal’s website.
View paper.