A series
of well-defined bifunctional dendrimers bearing one azide
and 5, 15, and 44 folate termini were synthesized via the divergent approach. Poly(N-isopropylacrylamide)
homopolymers PNIPAM-7k, PNIPAM-19k, and PNIPAM-64k were prepared using
the reversible addition-fragmentation chain-transfer polymerization
(60–67% yield) followed by end functionalization with a cyclooctyne
derivative. A grafting-to approach through strain-promoted azide alkyne
cycloaddition between the dendrimers and the PNIPAM afforded a series
of dendrimer-b-PNIPAM diblock copolymers containing
folates (G1-11k, G2-30k, and G3-95k). Investigation of the self-assembly
process in aqueous media revealed the formation of thermo- and pH-responsive
core–shell spherical micelles within the 70–160 nm size
range with low polydispersities. Within the nanoperiodic concept,
these dendrimer-b-PNIPAM copolymers behave as S1-type
nanoelements that self-assemble into soft:soft spherical nanocompounds
with a linear relationship between the molecular weight of the copolymers
and the hydrodynamic diameter of the self-assembled nanospheres. The
thermo- and pH-responsiveness of the micelles formed by the dendrimer-b-PNIPAM diblock copolymers bearing folates make them promising
candidates for targeted drug delivery.