Cubical Shape Enhances the Interaction of Layer-by-Layer Polymeric Particles with Breast Cancer Cells.
Cubical Shape Enhances the Interaction of Layer-by-Layer Polymeric Particles with Breast Cancer Cells.
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DOI：
10.1002/adhm.201500537
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发表时间：
2015-12-09
影响因子：
10
通讯作者：
Godin B
中科院分区：
文献类型：
--
作者：
Alexander JF;Kozlovskaya V;Chen J;Kuncewicz T;Kharlampieva E;Godin B
血液传播的物体呈非球形，其血流尺寸比血管内皮细胞开窗大得多，但在患病状态下，由于其弹性，能够穿过这些开窗。需要了解包括形状和弹性在内的物理参数在肿瘤微环境中发现的物体行为中的作用，以最终加强化疗并将其副作用降至最低。本研究探索了氢键单宁酸/聚(N-乙烯基吡咯烷酮)/(TA/PVPON)氢键单宁酸/聚(N-乙烯基吡咯烷酮)/(TA/PVPON)为中空聚合物壳的层层组装法制备的球形和立方体生物相容弹性微粒及其刚性核壳前驱体。与刚性5-双层(TA/PVPON)核壳不同，中空壳不被J774A.1巨噬细胞识别，但与内皮细胞和乳腺癌细胞相互作用。与球形外壳相比，HMVEC(内皮细胞)内化立方体外壳的效率分别是MDA-MB-231和SUM159(乳腺癌细胞)的5倍和6倍和2.5倍。在10 S−1(肿瘤血管特征)和10 0 S−1剪切速率(正常血管)下，立方体(TA/PVPON)5壳与内皮细胞的相互作用相似，而球形壳在10 S−1剪切速率下与内皮细胞的相互作用减弱。我们的数据表明，立方几何结构促进了颗粒与乳腺癌细胞的相互作用，而弹性则防止了肿瘤微环境中吞噬细胞的吞噬。
Blood-borne objects display a non-spherical shape with in-flow dimensions much larger than the vascular endothelial fenestrations, yet, at the diseased state, are able to traverse through these fenestrations owing to their elasticity. The role of physical parameters including shape and elasticity in the behavior of objects found in the tumor microenvironment needs to be understood to ultimately enhance chemotherapy and minimize its side-effects. In this study, sphere and cube-shaped biocompatible elastic microparticles (EM) made via layer-by-layer (LbL) assembly of hydrogen-bonded tannic acid/poly(N-vinylpyrrolidone)/ (TA/PVPON) as hollow polymer shells and their rigid core-shell precursors (RM) are explored. In contrast to rigid 5-bilayer (TA/PVPON) core-shells, hollow shells are unrecognized by J774A.1 macrophages yet interact with endothelial and breast cancer cells. Internalization of cubical shells by HMVEC (endothelial) is 5-fold more efficient and 6- and 2.5-fold more efficient for MDA-MB-231 and by SUM159 (breast cancer cells), respectively, compared to spherical shells. The interaction of cubical (TA/PVPON)5 shells with endothelial cells is similar under 10 s−1 (characteristic of tumor vasculature) and 100 s−1 shear rate (normal vasculature) while it is decreased at 100 s−1 shear rate for the spherical shells. Our data suggest that cubical geometry promotes interaction of particles with breast cancer cells, while elasticity prevents engulfment by phagocytic cells in the tumor microenvironment.