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
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.
引用
收藏
页码:1886 / 1896
页数:11
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