Yan Li-Tang, Yu Xiaobo
Physikalische Chemie II, Universität Bayreuth, D-95440 Bayreuth, Germany.
ACS Nano. 2009 Aug 25;3(8):2171-6. doi: 10.1021/nn9004236.
Dendrimers have successfully proved themselves as functional nanodevices for drug delivery because they can render drug molecules a greater water solubility, bioavailability, and biocompatibility. It has recently been suggested that the structural changes of cell membranes (e.g., local lipid density and actual pore or hole) could affect the permeability across them for dendrimers. However, to understand these effects requires direct measurements in a single cell and is thus very difficult and more challenging. Here we use mesoscopic simulations to investigate the tension-mediated complexes comprising charged dendrimers and lipid bilayer membranes. The structures of membranes are alternated by adjusting their surface tensions. Our simulations demonstrate that the permeability of charged dendrimers can be effectively enhanced in the tense membranes, and the permeability in the actual hole is several times higher than that in the lipid-poor section. The possible mechanism of charged dendrimer-induced pore nucleation in the tense membranes is evaluated. The findings have implications in tuning intracellular delivery rates and amounts in nanoscale complex and chemotherapeutics.
树枝状大分子已成功证明自身是用于药物递送的功能性纳米器件，因为它们能使药物分子具有更高的水溶性、生物利用度和生物相容性。最近有人提出，细胞膜的结构变化（如局部脂质密度以及实际的孔或洞）可能会影响树枝状大分子穿过细胞膜的通透性。然而，要了解这些影响需要在单个细胞中进行直接测量，因此非常困难且更具挑战性。在这里，我们使用介观模拟来研究由带电树枝状大分子和脂质双层膜组成的张力介导复合物。通过调节膜的表面张力来改变膜的结构。我们的模拟表明，在张力膜中带电树枝状大分子的通透性可有效提高，且在实际的孔中的通透性比脂质贫乏区域的通透性高几倍。评估了带电树枝状大分子在张力膜中诱导孔形成的可能机制。这些发现对于调节纳米级复合物和化疗药物的细胞内递送速率及递送量具有重要意义。
