共 55 条
Stoichiometry and Structure of Poly(amidoamine) Dendrimer-Lipid Complexes
被引:86
作者:
Kelly, Christopher V.
[1
,2
,3
]
Liroff, Meghan G.
[3
,4
]
Triplett, L. Devon
[1
,3
]
Leroueil, Pascale R.
[3
,4
]
Mullen, Douglas G.
[3
]
Wallace, Joseph M.
[4
]
Meshinchi, Sasha
[5
]
Baker, James R., Jr.
[3
,6
]
Orr, Bradford G.
[1
,3
,7
]
Holl, Mark M. Banaszak
[1
,2
,3
,4
]
机构:
[1] Univ Michigan, Appl Phys Program, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Graham Environm Sustainabil Inst, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Michigan Nanotechnol Inst Med & Biol Sci, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Microscopy & Image Anal Lab, Ann Arbor, MI 48109 USA
[6] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA
[7] Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA
来源:
关键词:
poly(amidoamine) dendrimer;
phospholipid bilayer;
membrane disruption;
nanotoxicity;
membrane permeability;
PAMAM DENDRIMERS;
MOLECULAR-DYNAMICS;
PORE FORMATION;
POLYCATIONIC POLYMERS;
ULTRAFINE PARTICLES;
BILAYER DISRUPTION;
HOLE FORMATION;
DRUG-DELIVERY;
GENE DELIVERY;
NANOPARTICLES;
D O I:
10.1021/nn900173e
中图分类号:
O6 [化学];
学科分类号:
0703 ;
摘要:
The energetics, stoichiometry, and structure of poly(amidoamine) (PAMAM) dendrimer-phospholipid interactions were measured with isothermal titration calorimetry (ITC), transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS), and molecular dynamics (MD) simulations. Dendrimers of sixth-generation and smaller interacted with the lipids at an average stoichiometry and enthalpy proportional to the number of primary amines per dendrimers (4.5 +/- 0.1 lipids/primary amine and 6.3 +/- 0.3 kJ/mol of primary amines, respectively). Larger dendrimers, however, demonstrated a decreased number of bound lipids and heat release per primary amine, presumably due to the steric restriction of dendrimer deformation on the lipid bilayer. For example, eighth-generation PAMAM dendrimers bound to 44% fewer lipids per primary amine and released 63% less heat per primary amine as compared to the smaller dendrimers. These differences in binding stoichiometry support generation-dependent models for dendrimer-lipid complexation, which are consistent with previously observed generation-dependent differences in dendrimer-induced membrane disruption. Dendrimers of seventh-generation and larger bound to lipids with an average stoichiometry consistent with each dendrimer having been wrapped by a bilayer of lipids, whereas smaller dendrimers did not.
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页码:1886 / 1896
页数:11
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