Wednesday, November 01, 2006

From the Labs: Nanotechnology

Continued from page 1

By Kevin Bullis

Smart Nanosize Containers
Nanoparticles could signal when they are inside specific types of cells, leading to new diagnostic and treatment methods

Source: "Toward Intelligent Nanosize Bioreactors: A pH-Switchable, Channel-Equipped, Functional Polymer Nanocontainer"
Pavel Broz et al.
Nano Letters 6(10): 2349-2353

Results: Researchers in Switzerland have made 200-nanometer-wide containers dotted with pores whose walls are made of bacterial proteins. They demonstrated that these nano containers can control the location and duration of a fluorescent signal--lighting up only when the acidity of their environment matches that inside cell structures called lysosomes, which digest foreign materials that enter a cell.

Why it matters: The work shows that nanoparticles using active pores can respond to environmental cues, such as acidity, to perform useful functions. In one application, pH-sensitive nano carriers would light up only once they encountered lysosomes, ensuring that they'd reached the inside of cells. The researchers earlier showed that the carriers can latch onto particular types of cells, such as macrophages, suggesting that such a system could be used to identify specific cells in a lab sample. With some modifications, it could also be used to release a drug only inside targeted cells, making drug treatment more effective and reducing side effects by protecting nearby tissue.

Methods: Specially designed polymers combined with bacterial proteins self-assemble to form the containers, while added enzymes that break down certain compounds, causing them to fluoresce, are trapped inside. The pores' size prevents the enzymes from escaping but lets compounds gradually enter the container to be broken down, creating a long-lasting signal that is confined to the containers. The pH sensitivity is a result of two factors: the enzymes work best at lysosomal acidities, and the pores, which are open in most conditions, close at acid concentrations that are too high.

Next Steps: The research requires further tests to confirm that the nanoparticles work in living subjects. For potential drug-delivery applications, the researchers will pair drugs with specific cellular targets and develop a release mechanism; it could be based on synthetic pores that stay closed in neutral and alkaline environments as well as highly acidic ones, opening only in the particular pH range of the inside of a lysosome.