Enhancing radiotherapy by lipid nanocapsule-mediated delivery of amphiphilic gold nanoparticles to intracellular membranes

Yu Sang Yang, Randy Carney, Francesco Stellacci, Darrell J. Irvine

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Amphiphilic gold nanoparticles (amph-NPs), composed of gold cores surrounded by an amphiphilic mixed organic ligand shell, are capable of embedding within and traversing lipid membranes. Here we describe a strategy using crosslink-stabilized lipid nanocapsules (NCs) as carriers to transport such membrane-penetrating particles into tumor cells and promote their transfer to intracellular membranes for enhanced radiotherapy of cancer. We synthesized and characterized interbilayer-crosslinked multilamellar lipid vesicles (ICMVs) carrying amph-NPs embedded in the capsule walls, forming Au-NCs. Confocal and electron microscopies revealed that the intracellular distribution of amph-NPs within melanoma and breast tumor cells following uptake of free particles vs Au-NCs was quite distinct and that amph-NPs initially delivered into endosomes by Au-NCs transferred over a period of hours to intracellular membranes through tumor cells, with greater intracellular spread in melanoma cells than breast carcinoma cells. Clonogenic assays revealed that Au-NCs enhanced radiotherapeutic killing of melanoma cells. Thus, multilamellar lipid capsules may serve as an effective carrier to deliver amphiphilic gold nanoparticles to tumors, where the membrane-penetrating properties of these materials can significantly enhance the efficacy of frontline radiotherapy treatments.

Original languageEnglish (US)
Pages (from-to)8992-9002
Number of pages11
JournalACS Nano
Volume8
Issue number9
DOIs
StatePublished - Sep 23 2014
Externally publishedYes

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Keywords

  • amphiphilic nanoparticles
  • biological TEM
  • cell-penetrating nanoparticles
  • glycocalyx
  • gold nanoparticles
  • multilamellar lipid vesicles
  • radiotherapy

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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