Self-assembly of amphiphilic polymeric dendrimers synthesized with selective degradable linkages

Enhancing the structural complexity and functionality of building blocks allows the design and synthesis of complex macromolecular architectures. In this work, we use a combination of atom transfer radical polymerization to produce polymers with well-defined chain length and telechelic end group functionality and click reactions to quantitatively couple these polymer chains together to form functional second- and third-generation dendrimers. Importantly, this methodology provides starting polymers in combination with linkers and end group protecting chemistries to design dendrimers with degradable linkages between the desired generations and incorporates functionality at the polymer chain ends of each generation. We have synthesized second- and third- generation homo- and amphiphilic diblock copolymer dendrimers and specifically designed third-generation dendrimers in pure form such that the peripheral generational layer could be selectively cleaved off from the second-generation. The degradation of the peripheral polymer layer is a useful feature in biomedical delivery devices for slow and controlled release of its payload. These dendrimers also have either free or protected hydroxyl groups on the peripheral ends, which are useful for further chemical modification or chemical coupling to important biomolecules. The amphiphilic dendrimers self-assemble in water to form well-defined micelles of near identical size (18.2 nm, PDI = 1.04), each consisting of approximately 19 individual dendrimers. The dense core of the spherical micelles found from sizing measurements supports the postulate that these amphiphilic dendrimers have no mutual interpenetration and thus pack uniformly to form the micelles.