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 language | English (US) |
|---|---|
| Pages (from-to) | 8992-9002 |
| Number of pages | 11 |
| Journal | ACS Nano |
| Volume | 8 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 23 2014 |
| Externally published | Yes |
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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)
Cite this
Enhancing radiotherapy by lipid nanocapsule-mediated delivery of amphiphilic gold nanoparticles to intracellular membranes. / Yang, Yu Sang; Carney, Randy; Stellacci, Francesco; Irvine, Darrell J.
In: ACS Nano, Vol. 8, No. 9, 23.09.2014, p. 8992-9002.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhancing radiotherapy by lipid nanocapsule-mediated delivery of amphiphilic gold nanoparticles to intracellular membranes
AU - Yang, Yu Sang
AU - Carney, Randy
AU - Stellacci, Francesco
AU - Irvine, Darrell J.
PY - 2014/9/23
Y1 - 2014/9/23
N2 - 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.
AB - 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.
KW - amphiphilic nanoparticles
KW - biological TEM
KW - cell-penetrating nanoparticles
KW - glycocalyx
KW - gold nanoparticles
KW - multilamellar lipid vesicles
KW - radiotherapy
UR - http://www.scopus.com/inward/record.url?scp=84920407323&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84920407323&partnerID=8YFLogxK
U2 - 10.1021/nn502146r
DO - 10.1021/nn502146r
M3 - Article
C2 - 25123510
AN - SCOPUS:84920407323
VL - 8
SP - 8992
EP - 9002
JO - ACS Nano
JF - ACS Nano
SN - 1936-0851
IS - 9
ER -