Joined: 03 Oct 2005
|Posted: Thu Dec 08, 2005 10:52 am Post subject: Delivering Nanoparticle Drugs into Cells via Plant Molecules
|Singapore Scientists Use a Plant Molecule to Deliver Drug-Loaded Nanoparticles into Tumor Cells
For most drug delivery applications, delivering the therapeutic molecules to the surface of a tumor is only half the battle. Facilitating the transfer of drug into the cancer cell, across the formidable barrier of the cell membrane, is also important. Now, a research team at the National University of Singapore has identified one approach to improving the ability of drug-loaded nanoparticles to enter cells. The key to this new method is a well-studied, sugar-studded protein isolated from wheat germ.
Writing in the Journal of Controlled Release, Kee-Yong Lim, Ph.D., and her former graduate student Yun Mo, Ph.D., describe their use of the molecule known as “wheat germ agglutinin” as a means of getting polymer nanoparticles into tumor cells. Wheat germ agglutinin belongs to a family of naturally occurring compounds called lectins that bind to specific sugar molecules on cell surfaces. Research performed over 30 years ago showed that wheat germ agglutinin in particular binds preferentially to sugar molecules that are found on many types of tumor cells, including leukemia cells and lung cancer cells, and earlier work by Dr. Lim and her colleagues showed that cells would engulf nanoparticles covered with wheat germ agglutinin.
To determine if wheat germ agglutinin could help get more drug inside tumor cells, Drs. Lim and Mo first mixed the biocompatible polymer PLGA with the anticancer drug paclitaxel in such a way as to form drug-loaded nanoparticles. They then were able to coat these nanoparticles with wheat germ agglutinin using a mild chemical reaction. After purifying the resulting nanoparticles, the investigators then added them to lung cancer cells growing in tissue culture dishes. For comparison’s sake, the researchers performed control experiments in which they treated other cells with paclitaxel-loaded nanoparticles lacking the wheat germ agglutinin coating and treated non-cancerous cells with the targeted nanoparticles.
The results of these experiments showed that the wheat germ agglutinin had a substantial effect on nanoparticle uptake into cells and the subsequent release of paclitaxel within the tumor cells. Tumor cells not only took up more of the targeted nanoparticles compared to the untargeted nanoparticles, but also engulfed up to 10 times more of the labeled nanoparticles than did non-cancerous cells. As a result, paclitaxel-loaded nanoparticles targeted with wheat germ agglutinin killed far more cancer cells than non-cancer cells, and were also better at killing tumor cells than either untargeted nanoparticles or paclitaxel itself.
Based on these results, the investigators conducted a follow-up experiment in which they injected their nanoparticles directly into tumors growing in mice. A single injection of the targeted nanoparticles stopped tumor growth for at least 25 days, while tumors injected with paclitaxel alone doubled in size in 11 days.
This work is detailed in a paper titled, “Paclitaxel-loaded PLGA nanoparticles: Potentiation of anticancer activity by surface conjugation with wheat germ agglutinin.” An abstract is available through PubMed.
Source: NCI Alliance for Nanotechnology in Cancer.
This story was posted on 7 December 2005.