"Our interest is in controlling and directing the delivery of drugs at the sub-cellular level," Dusica Maysinger of McGill told nanotechweb.org. "As one of the first steps, we have investigated the sub-cellular distribution of fluorescently labelled micelles."

Block copolymer micelles are typically made up of amphiphilic copolymers, which are polymers that contain both hydrophobic and hydrophilic components. The micelles, which form once a critical concentration is reached, have a core-shell-type architecture: the hydrophobic components assemble around the core while the hydrophilic components form a protective shell, or corona. The corona ensures that the micelles are soluble in water, while the hollow core can accommodate hydrophobic drugs.

In this work, Maysinger and colleagues used micelles made from poly(caprolactone)-b-poly(ethylene oxide), otherwise known as PCL-b-PEO. These micelles were spherical with diameters of 20-45 nm. The scientists labelled them with fluorescent tetramethylrhodamine-5-carbonyl azide (TMRCA) molecules attached to the hydrophobic PCL end of the polymer.

Maysinger and the team then examined the distribution of the labelled micelles inside rat pheochromocytoma cells. Fluorescence was detectable from the micelles in the cell cytoplasm - in cytoplasmic organelles such as mitochondria and the Golgi apparatus - but not in the cell nucleus. According to the researchers, this is relevant for the delivery of inhibitors and activators of the cell-signalling pathways that are commonly activated in the cytoplasmic compartment.

The team also compared the distribution inside PC12 cells of labelled micelles containing the membrane-selective dye DAF with the distribution of free DAF. Using micelles increased the amount of DAF delivered to the cell.

"We can change the target site, mode of internalization and increase the concentration of the drug in subcellular organelles when we use micelles," said Maysinger. "The applications of our micelles are geared towards the local delivery of immunosupressants in transplantations of islets of Langerhans [pancreatic tissue] in diabetes, as well as the delivery of anticancer agents, and androgens and oestrogens in hormonal disorders."

Now Maysinger and colleagues are "investigating polymers with active moieties targeting particular organelles, incorporating drugs that locally affect the cell signalling and refining the detection of delivery systems by using gold and fluorescent labelled polymers."

The researchers reported their work in Science.