Nanomaterials provide a potential platform for cancer treatment, with applications from technologies that simultaneously detect early stage cancers, target cancer cells over non-cancerous cells, directly deliver an active anti-cancer therapeutic, and monitor treatment efficacy. Polyamidoamine (PAMAM) dendrimers are a class of nanomaterials ideally suited for use as a drug delivery platform due to their controllable size, uniformity, and ample number of versatile terminal amine groups that allow for effective conjugation reactions. Thus, functionalizing dendritic polymers with small-molecule conjugates yields nanomaterials having the relevant characteristics for treating cancer with greater selectivity and efficacy. To this end, dendrimers conjugated with targeting agents, dyes, and anti-cancer drugs have been used to track and selectively deliver chemotherapeutics to tumor cells. Due to their high number of conjugation sites, conjugated dendrimer products can result in a distribution of populations varying in the ratio of small molecules per dendrimer. This distribution includes a population of a non-functionalized dendrimer which may decrease efficiency of the nanotherapeutic. The distribution also contains a highly conjugated population that would increase toxicity in the cell. In this study the dyes 5-TRITC and 5-TAMRA were conjugated to a generation 3 (G3) dendrimer at various ratios of dye to dendrimer under varying conditions in order to minimize the amount of non-functionalized material. The G3-TAMRA products were further separated by HPLC to isolate the different populations of dendrimer conjugates. The conjugates will be analyzed to determine whether the monodisperse material with an exact number of small molecule conjugate exhibits greater cellular uptake compared to a polydisperse material with a distribution of populations including the non-functionalized material.

Synthesis, isolation, and characterization of monodisperse nanotherapeutics as potential chemotherapy delivery systems

243rd National Meeting (2012)

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