title: Enhancing radiotherapy by lipid nanocapsule-mediated delivery of amphiphilic gold nanoparticles to intracellular membranes.
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.
authors.affiliation: Department of Materials Science and Engineering, ‡Department of Biological Engineering, ⊥Institute for Soldier Nanotechnologies, and #Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Yu-Sang
authors.initials: YS
authors.lastname: Yang
authors.forename: Randy P
authors.initials: RP
authors.lastname: Carney
authors.forename: Francesco
authors.initials: F
authors.lastname: Stellacci
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Irvine
mesh_terms: D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D006046:Gold / Q000737:chemistry / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D007425:Intracellular Membranes / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D008546:Melanoma, Experimental / Q000473:pathology / Q000532:radiotherapy*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice
chemical_list: D004337:Drug Carriers; D008055:Lipids; D006046:Gold
keywords: amphiphilic nanoparticles; biological TEM; cell-penetrating nanoparticles; glycocalyx; gold nanoparticles; multilamellar lipid vesicles; radiotherapy