DEFINITION OF BIONANOTECHNOLOGY

At the present time, there is no consensus definition of bionanotechnology. To take advantage of the enthusiasm of funding agencies, a number of old (and important) areas, such as colloid science, molecular biology, and implantable materials surface science, have been relabeled “nanotechnology.” In fact, all of these fields, coupled with biological systems, should be included in bionanotechnology. In general, the idea of bionanotechnology is the engineering of interfaces between molecules or materials and biological systems. Looking ahead, the key areas for commercialization will be bringing engineered systems into biological contact and biological function.

The version of bionanotechnology popularized in the media has been largely oversold. The general idea, which was popular 20 years ago as the “magic-bullet” theory of biotechnology and has been adopted as the bionanotechnology target, can be described as the “dump truck” model of technology. In this conception, the technology components consist of a targeting moiety, either biological or nanotechnological, and one or more cargoes, which are envisioned as small machines capable of specific destructive or corrective action.

In reality, designing targeting molecules that are selective for diseased tissues and capable of delivering cargoes larger than a typical antibody has proven extraordinarily difficult, and molecular targeting of nanoscale devices greater than 5 nm outside the vascular space may prove to be prohibitively difficult. However, with no guiding principles for the effective biological direction of nonbiological molecules, this is still an open question.

In this paper, I describe three recent examples of commercialized bionanotechnology, beginning with the one that is the best characterized system. The three are antibody-directed enzyme prodrug therapy (ADEPT), superparamagnetic iron oxide particles for enhancing contrast on magnetic resonance images (MRIs), and quantum-dot technology for biological detection. Each of these shows the potential power and some of the challenges of integrating technologies at the molecular level.

ANTIBODY-DIRECTED ENZYME PRODRUG THERAPY

Perhaps the most salient and relevant example of a bionanotechnology currently being commercialized is the ADEPT method being investigated by Genencor and Seattle Genetics (Figure 1). In this method, an antibody-enzyme fusion is first prepared and isolated. This molecule can be designed with precise chemical (biological) composition, precise linkage geometry, and complete definition and characterization using standard molecular-biology techniques and biochemical methods. The antibody, linked to the enzyme, can be used to target the particular antibody-enzyme conjugate to the site of interest. In this way, a small antibody fragment is used to target a molecular machine (an enzyme) to a par-



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