Enhancing Radiotherapy by Lipid Nanocapsule-Mediated Delivery of Amphiphilic Gold Nanoparticles to Intracellular Membranes

• Main Authors: Yang, Yu-Sang Sabrina (Contributor), Carney, Randy P. (Author), Stellacci, Francesco (Author), Irvine, Darrell J. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Institute for Soldier Nanotechnologies (Contributor), Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Materials Science and Engineering (Contributor), Ragon Institute of MGH, MIT and Harvard (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor)
• Format: Article
• Language: English
• Published: American Chemical Society (ACS), 2015-10-23T17:12:00Z.
• Subjects: Article
• Online Access: Get fulltext

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.
United States. Army Research Office (Contract W911NF-13-D-0001)
United States. Army Research Office (Contract W911NF-07-D-0004)