science/technology 'Nanodumplings' eyed for DNA delivery Spherical particles that resemble Polish dumplings are cooking in the lab of Karen L. Wooley, an assistant professor of chem istry at Washington University, St. Louis. Wooley believes they can be used to deliv er DNA in gene therapy applications. The spheres feature a hydrophilic shell enclosing a hydrophobic core. The mor phology reminded one of Wooley's col leagues, Tomasz Kowalewski, of knedels—a Polish food made of meat encased in dough. That's why the particles are also called shell-cross-linked knedels (SCKs). Hydrophilic shell/hydrophobic core structures have many applications, espe cially in drug delivery, and researchers prepare them in various ways, for exam ple, with unimolecular micelles (C&EN, Jan. 18, page 63). Wooley's approach in volves cross-linking polymeric micelles in such a way that the links are formed only in the hydrophilic shell. The approach mimics the assembly of folded proteins. "We rely on self-assembly based on weak interactions to prepare the micelles," she explains. "Then we stabilize them through covalent linkages." SCKs have nanoscale dimensions, mak ing it possible to take biomimicry to an other level. "We're looking at how the nanoparticles can mimic biological species in terms of biological function, for exam ple, by binding or encapsulating DNA," Wooley says. "Although we're currently early in the investigation, the nanoparticle development is basically building up for gene therapy applications. "We want to use these as DNA carri ers. We think we can condense the DNA into the small volume of the particles, transport the particles to the cell, and have them release the DNA once they're inside the cell." Working with graduate students K. Bruce Thurmond II and Qinggao Ma, Wooley has been attempting to mimic histones. These are proteins that DNA wraps around. The electrostatic interactions be tween the phosphate groups in DNA and the basic residues in the histones help compact DNA, making it possible to con tain the human genome, for example, in a space of only 10 um diameter. "There's a lot of work being done on binding proteins to polymers and how that binding can condense DNA to a smaller volume for gene therapy," Wool ey says. "What we've done is mimic the histone core more closely. We make 38 FEBRUARY 8, 1999 C&EN
nanospheres that are about the size of the histone core, and we're mimicking both electrostatic surface interaction and particle size in trying to assemble the DNA in a particular fashion." Using dynamic light-scattering and DNA-cleaving experiments, Wooley's group has found that DNA molecules ag gregate around 15-nm-diameter SCKs and that the aggregation protects the DNA molecules from cleavage by enzymes. Changes in the diameter of the aggre gates also hint at DNA compaction, pre sumably through electrostatic interaction between the SCK surface and DNA. What would be even better is to have individual SCKs encapsulate DNA, just like the protein coat surrounding the Atomic force microscopy image DNA or RNA of viruses. "Then we can at bottom reveals nanoscale dimensions have uniform size and structure con of knedels with a polystyrene core trolled by a stable membranelike shell of surrounded by a cross-linked, quaternized nanoscale dimension," Wooley says. poly(4-vinylpyridine) shell. To convert SCKs to nanocapsules mim icking the virus protein coat, the cores "Now we have to get to the level where we must be removed. Wooley's group has can actually bring DNA into the structure." Maureen Rouhi demonstrated core removal from SCKs.
Luminaries highlight chemistry's contributions A number of luminaries in the chemical sciences attending the Wide World of Chemistry symposium at the American Association for the Advancement of Sci ence's (AAAS) annual meeting last month in Anaheim, Calif., reemphasized that chemistry is one of the most far-reaching and important disciplines in the world. In fact, "chemistry has become its own global village," said American Chemical Society President Ed Wasserman. Wasserman called for increased in teraction between AAAS and ACS— pointing out that while biotechnology and medicine are the largest AAAS divi sions, they're based on chemistry. Organized by Helen M. Free, ACS Re gion II director, and Jeffrey Aube, a me dicinal chemistry professor at the Univer sity of Kansas, Lawrence, the symposium
aired what's being done to continue to spread the gospel of chemistry. The ses sion was moderated by Peter Beak, a chemistry professor at the University of Illinois, Urbana-Champaign. Free and Ned D. Heindel, both ACS past presidents, gave an overview of the International Chemistry Celebration (IChC), a year of promotion that began last November. IChC's purpose is to bring the world's attention to chemistry. Mary Bullock, special projects head at the National Science Foundation, de scribed that agency's contributions to IChC; Sylvia A. Ware, director of ACS's Education Division, described global ef forts in science education reform; and ACS Immediate Past-President Paul S. Anderson talked about drug discovery. Mary L. Good, president-elect of AAAS and a past ACS president, Β summarized chemistry's I ubiquitous influence on | the global economy. I Good pointed out that in % 1995, 50% of industrial sci•§ entists and engineers were ^ chemists and chemical engi neers. "We don't talk about it, we don't take advantage of it, but we drive industry," she said. From left, Anderson, Bullock, Wasserman, Free, Beak, Elizabeth Wilson Good, Heindel, and Ware at the AAAS symposium.
