Determining molecular mass distributions and compositions of functionalized dendrimer nanoparticles

This study demonstrates that a combination of unconventional electron microscopy techniques provides a quantitative means of assessing the degree of monodispersity of gadolinium (Gd) diethylenetriamine pentaacetic acid-conjugated polyamidoamine (PAMAM) dendrimers, which are designed for diagnostic imaging and delivering chemotherapeutics. Specifically, analysis of images acquired in the scanning transmission electron microscopy mode yields the distribution of molecular weights of individual dendrimers, whereas analysis of images acquired in the energy-filtering transmission electron microscopy mode yields the distribution of Gd atoms bound to the dendrimer nanoparticles. Measured compositions of Gd-conjugated G7 and G8 PAMAM dendrimers were consistent with the known synthetic chemistry. The G7 dendrimers had a mass of 330 +/- 4 kDa and 266 +/- 4 Gd atoms (+/- standard error of the mean). The G8 dendrimers had a mass of 600 +/- 8 kDa and 350 +/- 5 Gd atoms (+/- standard error of the mean). This approach will be particularly attractive for assessing the mass, composition and homogeneity of metal-containing organic nanoparticles used in nanomedicine.