Tiny Trojan Horse Targets Tumors - How to Build a Heat-Sensitive Liposome

by Monte Basgall

Liposomes are tiny capsules made of lipids, the same fatty molecules that make up the membrane of every cell in the body. These synthetic spheres naturally tend to form into hollow capsules around a drop of watery solution.

liposomesResearchers first fabricated liposomes in 1965 but needed several decades to give them protection against attack by the body’s immune system. Today, they’re coated in polyethylene glycol, which provides several hours of protection in the bloodstream.

David Needham’s years of tinkering have resulted in a nanosphere that also tears open to release drugs at precisely 105 degrees Fahrenheit.

The sphere is just one hundred nanometers, or 100 millionths of a meter in diameter — tiny next to a human cell. Visible only through electron microscopes, it’s made of two types of molecules collectively known as phospholipids.

“That’s the same material nature chose to make cell membranes, so it is very biocompatible,” Needham says.

These particular phospholipids naturally self-assemble into a soccer ball shape that will melt like candle wax along the ball’s “stitches” when heated up to just a few degrees above body temperature. Such slight warming will not harm healthy tissues, but it will unleash the nanocapsule’s cargo — doxorubicin — a powerful drug that can devastate tumors and their supporting blood vessels.

Getting the drug into the tiny spheres relies on a method developed years ago by others, Needham says. When the capsule is made more acidic inside than outside, the slightly basic doxorubicin will be automatically pulled inside.

Their tiny size allows liposomes to roam the bloodstream, including vessels that supply tumors. When they reach a tumor that is being slightly heated by a focused beam of microwave energy, the deadly cargo is released. (See a Windows Media video animation created by Celsion Corp.)

Such pinpoint delivery confines the drug to the tumor and its blood vessels. Lipsomes that don’t reach the target with their cargoes are eventually filtered out and destroyed in the liver.

“The liver is a great garbage dump,” Needham says.