Tailoring dendrimer conjugates for biomedical applications: the impact of altering hydrophobicity

Hydrophobicity is known to play a key role in the biological distribution of materials but is often an overlooked parameter when conjugating targeting agents, drugs, and dyes to dendrimers. This review examines the impact of hydrophobic variation in stochastically conjugated dendrimers as well as materials where synthetic methods or approaches to purification provide more controlled samples. Hydrophobic interactions are considered for three general classes: (1) terminal functional group modifications, (2) bioactive small molecules chosen to interact with receptors and proteins as targeting agents and/or drugs, and (3) imaging agents to track biological activity. Impacts on membrane interaction and cellular uptake, biodistribution, interaction with transport proteins, and pharmacokinetics are discussed. The size range of the dendrimers discussed is ~ 1–10 nm.