Sugar-Coated Nanomachines Cure Cancer
An idea going back to Fantastic Voyage is that physicians can shrink to microscopic size and travel through the blood vessels to treat the site of a patient’s illness. Today, we’re not shrinking human physicians, but nanomachines. This research team at University of Tokyo focuses on a particular challenge for nanomedicine, getting the therapeutic agents across the blood brain barrier. The blood brain barrier is especially challenging to fight brain tumors, such as glioblastoma, the kind that Senator McCain had. Dr. Kataoka discusses his work here.
Kataoka’s group used an ingenious trick to get their device across the blood vessel membrane. The capillaries into the brain exclude lots of things, but need nutrients—especially the sugar called glucose. The brain has one of the highest glucose uptake rates found in the body. The glucose is taken up by a protein called GLUT1 that is embedded in the membrane of the capillary cells. So the researchers built a delivery device called a “micelle” (basically a highly engineered soap bubble). The micelle contains sugar molecules attached to a carbon chaine (hydrocarbon) that dissolves into the micelle membrane. Now the whole sugar-coated object can bind to GLUT1 molecules in the capillary, and dissolve through the membrane.
How do we know it works? This micrograph shows the capillaries within the brain of a mouse. The sugar-coated micelles have a tagged molecule that fluoresces red. In the first image, we see the micelles only found within the capillary vessels. But after 60 minutes, the micelles have leaked out of the vessels into the surrounding tissue; a process known by a mouthfull of a term, “extravasation.” Extravasation is something that white blood cells normally do all the time, in most parts of the body, but not the brain.
If that’s not strange enough, at ICFA “Clone with Joan” Saturday breakfast we’ll hear more about how gut bacteria may take up residence in the brain (a controversial report) and how bacteria can treat human genetic diseases. Sounds more and more like the microbial aliens of Brain Plague.
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It’s a sugar pill! This technique does seem like a good way to deliver drugs, biologicals, and even viruses or engineered bacteria across the blood-brain barrier to treat neurological diseases.
Great to hear from you, Alex! What’s new?
Ironically, sugar transport is one of the oldest medical therapies for oral rehydration; it drives sodium cotransport for water recovery during cholera, for example.