Multifunctional trackable dendritic scaffolds and delivery agents.

Dendrimers and other three-dimensional molecular assemblies are attractive scaffolds for biological delivery agents and diagnostic probes due to their globular shape, modular structure, monodispersity, and plurality of functional end groups. To address this potential, a number of strategies and related dendritic architectures have been developed for delivery of bioactive molecules to desired cells or tissue, with encapsulation and covalent attachment to the dendritic chain ends being two major approaches. While the encapsulation of drugs or dyes within the inner cavities of the dendrimer is promising, in most cases only a limited number of guest molecules can be encapsulated even with dendrimers of high generations. Moreover, the noncovalent nature of the encapsulation makes it a challenge to control the stability of the loaded carrier and subsequent release of the payload. An alternative strategy exploits the large number of dendritic chain ends to carry the cargo molecules. However, loading of large amounts of hydrophobic drugs or dyes can alter the dendrimer surface properties and decrease its solubility and bio-compatibility. Partial functionalization alleviates this issue but results in random chain-end modification leading to a dispersity in loading, variable bio-performance, and in many cases only low degrees of surface functionalization can be achieved without significantly changing the surface properties. In order to maintain both high loading and monodispersity, an alternative design is to covalently attach the cargo molecules to the interior of the dendrimer. This strategy overcomes the challenges associated with surface functionalization, allowing high and reproducible loading without significantly altering the surface properties of the dendritic scaffold. To illustrate the power of this novel strategy, we report an accelerated synthesis of orthogonal surface and internally functionalized dendrimers and their application as multifunctional dendritic scaffolds (Figure 1). As model