The structure of a series of poly(amidoamine) dendrimers Gn(C12) generated from a diaminododecane core have been investigated using the photophysical properties of an external dye, nile red. The modified dendrimers Gn(C12) show the ability to host the hydrophobic dye, nile red, in aqueous solution. The ability of Gn(C12) to host nile red has been compared to corresponding amino-core Gn(NH3) and diaminoethane-core Gn(C2) dendrimers of the same generation size. The emission of nile red in aqueous media is significantly enhanced in the presence of Gn(C12) and not at all for Gn(NH3) and Gn(C2). These results imply a strong tendency for the nile red probe to associate with the long methylene chain of the modified dendrimers in aqueous solutions. Moreover, the interactions of these dendrimers with anionic surfactants generate supramolecular assemblies which greatly enhance their ability to accomodate the nile red. Fluorescence polarization and emission as a function of pH were also studied in an effort to elucidate the interaction of the nile red probe with the dendrimer−surfactant assemblies.

The spatial distribution of the terminal groups of poly(amido amine) dendrimers have been determined experimentally by small-angle neutron scattering with deuterium labeling and scattering contrast variation. The radius of gyration of deuterated terminal units of generation 7 dendrimers is 39.3 ± 1.0 Å. This is significantly larger than the radius of gyration of the whole dendrimer, which is 34.4 ± 0.2 Å. These data indicate that dendrimers have terminal groups that are concentrated near the periphery. These results are inconsistent with many computer simulations and some molecular models.

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As small-animal fluorescence imaging becomes increasingly accessible to a broad spectrum of users, many lab animal researchers are just beginning to be exposed to its challenges. One setback to fluorescence imaging is background autofluorescence generated in animal tissue and in ingested food. The authors bring this issue into focus, and show how autofluorescence can be reduced in nude mice through selection of appropriate excitation wavelength and mouse diet.

Gene-directed enzyme prodrug therapy (GDEPT) is a promising and emerging strategy that attempts to limit the systemic toxicity inherent to cancer chemotherapy by means of tumor-targeted delivery and expression of an exogenous gene whose product converts nontoxic prodrug(s) into activated cytotoxic agent(s). The bacterial nitroreductase (NTR) enzyme, coupled with its substrate prodrug 5-(azaridin-1-yl)-2,4-dinitrobenzamide (CB1954), is a promising GDEPT strategy that has reached clinical trials. However, no strategy exists to visually monitor and quantitatively evaluate the therapeutic efficacy of NTR/CB1954 prodrug therapy in cells and imaging in living animals. As the success of any GDEPT is dependent upon the efficiency of transgene expression in vivo, we developed a safe, sensitive and reproducible noninvasive imaging method to monitor NTR transgene expression that would allow quantitative assessment of both therapeutic efficacy and diagnostic outcome of NTR/ CB1954 prodrug therapy in the future. Here, we investigate the use of a novel fluorescent imaging dye CytoCy5S (a Cy5-labeled quenched substrate of NTR enzyme) on various cancer cell lines in vitro and in NTR-transfected tumor-bearing animals in vivo. CytoCy5S-labeled cells become fluorescent at 'red-shifted' wavelengths (638 nm) when reduced by cellular NTR enzyme and remains trapped within the cells for extended periods of time. The conversion and entrapment was dynamically recorded using a time-lapsed microscopy. Systemic and intratumoral delivery of CytoCy5S to NTR-expressing tumors in animals indicated steady and reproducible signals even 16 h after delivery (Po0.001). This is the first study to address visual monitoring and quantitative evaluation of NTR activity in small animals using CytoCy5S, and establishes the capability of NTR to function as an imageable reporter gene.

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Dendritic polymers, or dendrimers, represent a new class of macromolecules characterized by an ultra-branched molecular architecture generated by a novel synthetic route developed in the mid-1980s. As the synthetic science of these molecules matures, the search for ways to use them in military and commercial technologies is becoming increasingly active. However, a lack of physical property data has made the identification of suitable application and technology areas that are ripe for exploitation of dendrimers difficult. The purpose of this series of reports is to compile, in the most concise form possible, some fundamental physical property information about dendrimers. The focus is on the behavior of poly(amidoamine) or PAMAM dendrimers, which are produced domestically by Dendritech, Inc., of Midland, Michigan. In this first report, the properties of mid-size, "Generation 5," PAMAM dendrimers are highlighted. The second and third reports will focus on the generation or size dependence of the physical properties of PAMAM dendrimers and on the end-group chemistry dependence of PAMAM dendrimers, respectively. INTENTIONALLY LEFT BLANK VI