Kinetic analysis of the interaction between poly(amidoamine) dendrimers and model lipid membranes.

Kinetic analysis of the interaction between poly(amidoamine) dendrimers and model lipid membranes.
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DOI:
10.1016/j.bbamem.2010.08.017
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发表时间:
2011
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
V. Tiriveedhi;Kelly M. Kitchens;Kerrick J Nevels;H. Ghandehari;P. Butko
V. Tiriveedhi;Kelly M. Kitchens;Kerrick J Nevels;H. Ghandehari;P. Butko
中科院分区:
其他
文献类型:
--
作者:
V. Tiriveedhi;Kelly M. Kitchens;Kerrick J Nevels;H. Ghandehari;P. Butko

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我们使用荧光光谱和表面张力法研究低代(G1和G4)聚(酰胺胺)(PAMAM)树枝状聚合物,细胞内药物递送的潜在车辆,和模型脂质双层之间的相互作用。膜协会的荧光标记的树枝状聚合物,测量荧光各向异性,增加的树枝状聚合物的大小和增加的负电荷密度在膜中,表明静电相互作用的性质。当膜掺杂有芘标记的磷脂酰甘油(pyrene-PG)时,当膜处于液晶状态时,芘准分子荧光显示树枝状聚合物诱导的带负电荷的脂质的选择性聚集。一个非线性的Stern-Volmer猝灭树枝状大分子的荧光与溴化钴建议树枝状大分子诱导的脂质囊泡的聚集,这增加了树枝状大分子的代数。表面张力测量表明,树枝状聚合物仅在亚生理表面压力(<30 mN/m)下渗透到脂质单层中。我们得出结论,低代PAMAM树枝状聚合物与脂膜主要是静电,而不会显着损害双层的完整性。它们与具有更高流动性和更低表面压力的膜结合更强,这是快速分裂细胞的特征。
We used fluorescence spectroscopy and surface tensiometry to study the interaction between low-generation (G1 and G4) poly(amidoamine) (PAMAM) dendrimers, potential vehicles for intracellular drug delivery, and model lipid bilayers. Membrane association of fluorescently labeled dendrimers, measured by fluorescence anisotropy, increased with increasing size of the dendrimer and with increasing negative charge density in the membrane, indicating the electrostatic nature of the interaction. When the membrane was doped with pyrene-labeled phosphatidyl glycerol (pyrene-PG), pyrene excimer fluorescence demonstrated a dendrimer-induced selective aggregation of negatively charged lipids when the membrane was in the liquid crystalline state. A nonlinear Stern–Volmer quenching of dendrimer fluorescence with cobalt bromide suggested a dendrimer-induced aggregation of lipid vesicles, which increased with the dendrimer's generation number. Surface tensiometry measurements showed that dendrimers penetrated into the lipid monolayer only at subphysiologic surface pressures (<30mN/m). We conclude that the low-generation PAMAM dendrimers associate with lipid membranes predominantly electrostatically, without significantly compromising the bilayer integrity. They bind stronger to membranes with higher fluidity and lower surface pressure, which are characteristic of rapidly dividing cells.