The generation of dendrimers is a powerful tool in the control of the size and biodistribution of polyion complexes (PIC). Using a combinatorial screening of six dendrimers (18-243 terminal groups) and five oppositely charged PEGylated copolymers, a dendrimer-to-PIC hierarchical transfer of structural information was revealed with PIC diameters that increased from 80 to 500 nm on decreasing the dendrimer generation. This rise in size, which was also accompanied by a micelle-to-vesicle transition, is interpreted according to a cone- to rod-shaped progression in the architecture of the unit PIC (uPIC). This precise size tuning enabled dendritic PICs to act as nanorulers for controlled biodistribution. Overall, a domino-like control of the size and biological properties of PIC that is not attainable with linear polymers is feasible through dendrimer generation.
A multigram synthesis of the repeating unit of GATG (gallic acid-triethylene glycol) dendrimers is described through an efficient and cost-effective route. These conditions overcome major problems precluding scaling up and afford product in excellent overall yield and purity. Special attention has been paid in this process to green chemistry principles: atom economy, safety, and waste reduction. This scheme could be easily adapted for the preparation of similar dendritic systems.
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