Dendritic polymer nanoparticles (NPs) are promising vehicles
for
drug delivery. Most dendrimer polymer NPs, however, exhibit positive
surface charge which make them, in many instances, cytotoxic. We constructed
noncationic, amphiphilic dendrimer NPs embedding curcumin and resveratrol,
natural polyphenols exhibiting anticancer properties. The curcumin/resveratrol/dendrimer
NPs both effectively shielded the embedded polyphenols and facilitated
their slow release and, notably, targeted cancer cells. The experimental
data trace the cancer cell toxicity of the curcumin/resveratrol/dendrimer
NPs to impairment of mitochondrial functions, specifically giving
rise to enhanced intracellular calcium release, inhibition of cytochrome c oxidase enzyme activity, decreased mitochondrial membrane
potential, and mitochondrial membrane perturbation. Importantly, synergism
between the dendrimer-NP-embedded curcumin and resveratrol was observed,
as more pronounced cancer cell death and mitochondrial disruption
were induced by the curcumin/resveratrol/dendrimer NPs as compared
to either the freely dissolved polyphenols or amphiphilic dendrimer
NPs incorporating curcumin or resveratrol separately. This work suggests
that amphiphilic dendrimer NPs encapsulating curcumin and resveratrol
may constitute a promising anticancer therapeutic platform.