Science Editor

Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Researchers have spent years finding ways of using "nanomachines" (nanogram-scale crystals) to diagnose and image crystals in the body, and deliver drugs. Quantum nanodots ("qdots") are offered as attractive candidates for such technology because they glow, making it easy to track the minuscule payload particles.

A hybrid team of oncologists and bioengineers now reports success in targeting intravenous delivery of hybrid inorganic/organic molecules to specific tissues on a living mammal. Their report in the Proceedings of the National Academy of Sciences (PNAS) released online Sept. 10, 2002, is titled simply: "Nanocrystal targeting in vivo." The collaborating authors are at the Burnham Institute in La Jolla, Calif., and the University of California at San Diego.

Their paper describes how they injected mice in vivo with what they dub "qdots," each less than 10 nanometers in diameter, coated with short protein strands that home to preselected tissues - in their case, lung or breast cancerous tumors. The uncoated qdots have a diameter of 3.5 nanometers (glowing green) or 5.3 nm (red) - equivalent to about 40 kiloDaltons. The peptide coating adds another 150 kDs.

The authors programmed nanocrystalline, fluorescing, semiconductor qdots, and wrapped them inside minute peptide fragments that home to specific addresses inside living tissue. Then they injected these constructs into the tail veins of mice, postmarked for delivery to three different tissue addresses - tumors, blood vessels feeding tumors or the lymphatic ducts draining tumor tissue. After circulating in the bloodstream, the qdots clustered in the target area. Adding a coating of polyethylene glycol (PEG) prevented absorption of the particles by nontargeted tissues, such as liver or spleen.

Nanocrystals such as these, designed to flock to a specific tissue preselected disease site, and fluoresce or emit magnetic signals, could, the authors suggested, be used in future diagnostic systems or to deliver drugs directly to a disease site. "We did not observe any acute toxicity (i.e., overt thrombosis or signs of complement activation)," the paper noted, "even after 24 hours of circulation, caused by the intravenous administration of these nanoparticles."

A co-senior author of the PNAS paper commented, "We are enthusiastic about these results because we showed that qdots could be successfully used inside the body without causing blood clotting, and because the homing peptides directed them to a specific tumor type - in this case breast cancer."

The paper concluded: "Although the current nanosystems are rather simple, in the future we envision the fabrication of multifunctional nanosystems, known as nanomachines. Such devices may, as an example, sense the presence of disease, deliver a drug to its site and release the drug at that site."

Platelets Tango With von Willebrand Factor To Staunch Bleeding, Prevent Fatal Thrombosis

Platelets are irregularly shaped disklike fragments that frequent the peripheral blood, where they function in clotting. Platelets have no definite cell nucleus. They're half the size or less of a red blood cell, but contain no hemoglobin.

Yet people cannot live without platelets. They aggregate to seal leaks at sites of injury in the wall of damaged blood vessels. Plasma von Willebrand factor (VWF) acts as an extracellular adapter in this process, binding to collagen in the wounded wall, and then to a membrane glycoprotein called Iba (GP Iba ) on the platelet surface.

When this interaction can't happen, bleeding ensues, and fatal thrombosis may follow unless the hemorrhage can be staunched by feedback proteolysis of VWF. Soluble factor and platelets don't readily interact in the blood, but when platelets flow across a VWF-coated surface, they adhere rapidly and begin to roll along that surface. Von Willebrand disease is a bleeding disorder marked by increased binding of mutant VWF to GP Iba.

All of which leads to a paper in Science dated Aug. 16, 2002, and titled: "Structures of glycoprotein Iba and its complex with von Willebrand factor A1 domain." Its authors are structural chemists at the University of Utrecht in the Netherlands. The article concludes: "These detailed insights into the initial interactions in platelet adhesion suggest that GP1ba and VWF are attracted by long-range electrostatic interactions and indicate sites in the final complex, which present primary targets for development of drugs for the treatment or prevention of arterial thrombosis."

Bone Marrow Stem Cells, Slated For Pluripotent Tissue Generation, Let Down Their Researchers

Adult bone marrow stem cells are touted as progenitors of many organs and tissues in the body. This time they disappointed expectations of proliferating brain, kidney, gut and liver muscle. They seem less inclined to switch into other types of stem cells than some studies have suggested. Normally, hematopoietic stem cells in the bone marrow give rise to various types of blood cells.

A paper in Science released online Sept, 5, 2002, bears the title: "Little evidence for developmental plasticity of adult hematopoietic stem cells." Its authors are pathologists and developmental biologists at Stanford University School of Medicine.

Bug-Busting Enzyme Fends Off Larval Attack On Resistant Maize Plants

Certain strains of corn defend themselves against insect pests by producing a unique enzyme that weakens the stomach lining of caterpillars that feed on them. Scientists at Mississippi State University placed 4-day-old armyworm caterpillars on resistant strains of maize that produce an enzyme called 33-kD cysteine protease, plus susceptible strains that don't make the enzyme. Four days later, caterpillars that fed on susceptible plants were more than twice the size of larvae that munched on resistant plants.

The authors conclude that the enzyme "is a novel form of plant defense with potential applications in agricultural technology." Their report, in the Proceedings of the National Academy of Sciences (PNAS), released online Sept. 10, 2002, is titled: "Insect feeding mobilizes a unique plant defense protease that disrupts the peritrophic matrix of caterpillars."