No abstract

The ability of a dendritic shell to afford site isolation to a porphyrin core was evaluated using electron-transfer experiments with a series of porphyrin-core dendrimers. Cyclic voltammograms show that surrounding a porphyrin site with even a small generation (G ∼ 2) dendrimer can significantly lower the rate of interfacial electron transfer, ostensibly by decreasing the proximity of the porphyrin core to the electrode surface. This inhibition of electron transfer is more pronounced when larger generation dendrimers are employed. While a significant measure of site isolation is achieved with respect to an electrode surface, no hindrance to penetration of a small molecule is afforded by the dendritic shell surrounding the porphyrin core, an encouraging result if dendrimers are to be designed as macromolecular hosts with a functioning catalyst at the core. Stern-Volmer analysis was used to investigate the accessibility of a small molecule, benzylviologen, to the porphyrin core. For generations 1-3, the dendritic structure surrounding the porphyrin core does not significantly inhibit the ability of the viologen to quench the fluorescence of the metalloporphyrin. When the porphyrin is surrounded by fourth-generation dendrons, a slight rate enhancement was observed with quenching being 33% faster. Absorption and fluorescence spectroscopies of solutions of the porphyrin-core dendrimers also suggest that the dendrimeric surroundings do not interfere electrochemically or photophysically with the porphyrin core. The characteristic wavelengths of absorption and emission of the porphyrin moiety did not change as the dendrimer generation was increased, indicating that the dendritic substituents do not appear to significantly affect the electrochemical and photophysical nature of the metalloporphyrin core.

There has been increased interest in the use of polymeric nanoparticles as carriers for near-infrared (NIR) fluorescence dyes for cancer diagnosis. However, efficient delivery of nanoparticles to the tumors after systemic administration is limited by various biobarriers. In this study, we investigated the pharmacokinetics, biodistribution, and tumor uptake of sub-nanometer sized polymeric nanoparticles (<100 nm in diameter) coated with polyethylene glycol in tumor-bearing mice. To facility our studies, these particles were labeled with gamma emitter indium-111. We found that two NIRF nanoparticles having the same size (~20 nm) and chemical composition but different structures (i.e., hydrogel vs. core-shell nanolatex), or the same core-shell nanolatex particles with different sizes (20, 30, and 60 nm), had different blood circulation times, biodistribution, and tumor uptake. Interestingly, the tumor uptake of the nanolatex particles correlated well with their blood residence times (R 2 = 0.95), but similar correlations were not found between nanogel and nanolatex particles (R 2 = 0.05). These results suggest that both the blood circulation time and the extent of hydration of the nanoparticles play an important role in the tumor uptake of nanoparticles. Prolonged blood circulation of these NIRF nanoparticles allowed clear visualization of tumors with γ-scintigraphy and optical imaging after intravenous administration. A better understanding with regard to how the characteristics of nanoparticles influence their in vivo behavior is an important step towards designing NIRF nanoparticles suitable for molecular imaging applications and for efficient tumor delivery.

The preparation and modification of highly functionalized polyether dendrimers containing a versatile diethyl isophthalate terminal group is presented. The convergent synthesis consists of the construction of diester-terminated dendrons containing benzylic bromide functions at the focal point and their subsequent attachment to 4,4‘-biphenol cores. Dendrons up to the third generation can be prepared using recrystallization alone as the primary means of purification, allowing the synthesis to be performed on the scale of tens to hundreds of grams. The third and fourth generation bidendron dendrimers (with 32 and 64 terminal ester functionalities, respectively) have been subjected to a variety of surface modification reactions including hydrolysis, ester interchange, and amide−ester interchange, many of which proceed with complete conversion of the functional groups and in high isolated yield. The addition of alcohols such as benzyl alcohol or a first generation 3,5-di(benzyloxy)benzyl alcohol dendron to the dendrimer surface serves to increase the generation number of the dendrimers by one or two in what amounts to a “double convergent growth” approach. The analysis of these structurally precise dendrimers by matrix-assisted laser desorption ionization time of flight is described.