Synergistic Activity of Anticancer Polyphenols Embedded in Amphiphilic Dendrimer Nanoparticles

Shani Ben-Zichri, May Meltzer, Shiran Lacham-Hartman, Sofiya Kolusheva, Uzi Hadad, Niv Papo, Raz Jelinek

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)8913-8925
Number of pages13
JournalACS Applied Polymer Materials
Volume4
Issue number12
DOIs
StatePublished - 9 Dec 2022

Keywords

  • amphiphilic dendrimers
  • cancer
  • curcumin
  • dendrimer drug carriers
  • mitochondria
  • resveratrol

ASJC Scopus subject areas

  • Process Chemistry and Technology
  • Polymers and Plastics
  • Organic Chemistry

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