Shape Induced Inhibition of Phagocytosis of Polymer Particles

Shape Induced Inhibition of Phagocytosis of Polymer Particles
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DOI:
10.1007/s11095-008-9626-z
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发表时间:
2009-01-01
影响因子:
3.7
通讯作者:
Mitragotri, Samir
Mitragotri, Samir
中科院分区:
医学3区
文献类型:
--
作者:
Champion, Julie A.;Mitragotri, Samir

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为了确定颗粒形状是否可以被工程化以抑制巨噬细胞对药物递送颗粒的吞噬作用,巨噬细胞可以是成功治疗递送的显著障碍。大鼠肺泡巨噬细胞系用作模型巨噬细胞。利用延时视频显微镜和荧光显微镜评估颗粒的吞噬作用。我们制造了具有非常高的纵横比(> 20)的蠕虫状颗粒。与等体积的常规球形颗粒相比,这种形状表现出可忽略的吞噬作用。吞噬作用的减少是颗粒的高曲率区域减少到两个单点(蠕虫状颗粒的末端)的结果。内化仅在这些点是可能的,而附着在任何地方沿着的长度的颗粒抑制内化由于低曲率。我们已经创造了一个高纵横比的形状,表现出可忽略不计的巨噬细胞的吸收。
To determine if particle shape can be engineered to inhibit phagocytosis of drug delivery particles by macrophages, which can be a significant barrier to successful therapeutic delivery.Non-spherical polystyrene particles were fabricated by stretching spherical particles embedded in a polymer film. A rat alveolar macrophage cell line was used as model macrophages. Phagocytosis of particles was assessed using time-lapse video microscopy and fluorescence microscopy.We fabricated worm-like particles with very high aspect ratios (> 20). This shape exhibits negligible phagocytosis compared to conventional spherical particles of equal volume. Reduced phagocytosis is a result of decreasing high curvature regions of the particle to two single points, the ends of the worm-like particles. Internalization is possible only at these points, while attachment anywhere along the length of the particles inhibits internalization due to the low curvature.Shape-induced inhibition of phagocytosis of drug delivery particles is possible by minimizing the size-normalized curvature of particles. We have created a high aspect ratio shape that exhibits negligible uptake by macrophages.