Polymers constitute a diverse class
of macromolecules that have
demonstrated their unique advantages to be utilized for drug or gene
delivery applications. In particular, polymers with a highly ordered,
hyperbranched structure“dendrons”offer
significant benefits to the design of such nanomedicines. The incorporation
of dendrons into block copolymer micelles can endow various unique
properties that are not typically observed from linear polymer counterparts.
Specifically, the dendritic structure induces the conical shape of
unimers that form micelles, thereby improving the thermodynamic stability
and achieving a low critical micelle concentration (CMC). Furthermore,
through a high density of highly ordered functional groups, dendrons
can enhance gene complexation, drug loading, and stimuli-responsive
behavior. In addition, outward-branching dendrons can support a high
density of nonfouling polymers, such as poly(ethylene glycol), for
serum stability and variable densities of multifunctional groups for
multivalent cellular targeting and interactions. In this paper, we
review the design considerations for dendron–lipid nanoparticles
and dendron micelles formed from amphiphilic block copolymers intended
for gene transfection and cancer drug delivery applications. These
technologies are early in preclinical development and, as with other
nanomedicines, face many obstacles on the way to clinical adoption.
Nevertheless, the utility of dendron micelles for drug delivery remains
relatively underexplored, and we believe there are significant and
dramatic advancements to be made in tumor targeting with these platforms.