Red blood cell-like particles with the ability to avoid lung and spleen accumulation for the treatment of liver fibrosis
Red blood cell-like particles with the ability to avoid lung and spleen accumulation for the treatment of liver fibrosis
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DOI：
10.1016/j.biomaterials.2017.11.031
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发表时间：
2018-02-01
期刊：
影响因子：
14
通讯作者：
Yogo, Toshinobu
中科院分区：
文献类型：
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作者：
Hayashi, Koichiro;Yamada, Shota;Yogo, Toshinobu
微米大小的药物载体颗粒主要积聚在肺中，纳米大小的颗粒倾向于积聚在肝和脾中。在这里，我们表明，设计用于模拟红细胞（ABC）的微粒可以克服这些限制。在本研究中产生的RBC-MP具有独特的颗粒内弹性分布（IED），使它们能够围绕RBC样凹陷的中心轴弯曲，使它们能够穿过小于其直径的孔，机械地表现为真实的RBC。相比之下，球形MP（SPH-MP）和RBC-MP通过掺入硅氧烷网络（SiO2-RBC-MP）硬化，不能。除了IED，我们发现，变形能力也取决于形状和平均颗粒弹性。RBC-MP不会在肺和脾中积累，而是专门针对肝脏。与此相反，非RBC-MP如SPH-MP和SiO2-RBC-MP在肺和/或脾中显示出大量积累，并且非特异性地分散在各种器官中。因此，控制RBC-MP的形状和机械性质对于实现期望的生物分布是重要的。当RBC-MPs负载（TGF）-β受体抑制剂时，RBC-MPs可以治疗肝纤维化而不会产生肺毒性。(C)2017爱思唯尔有限公司版权所有
Micro-sized drug-carrier particles accumulate mainly in the lungs and nano-sized particles tend to accumulate in the liver and spleen. Here, we show that micro-particles designed to mimic red blood cells (ABCs) can overcome these limitations. The RBC-MPs created in this study have a unique intra-particle elasticity distribution (IED), enabling them to bend around the central axis of the RBC-like dent, enabling them to pass through pores smaller than their diameter, mechanically behaving as authentic RBCs. In contrast, spherical MPs (SPH-MPs) and RBC-MPs hardened by incorporating a siloxane network (SiO2-RBC-MPs), could not. In addition to the IED, we discovered that the deformability also depends on the shape and average particle elasticity. RBC-MPs did not accumulate in the lungs and the spleen, but were targeted specifically to the liver instead. In contrast, non-RBC-MPs such as SPH-MPs and SiO2-RBC-MPs showed heavy accumulation in the lungs and/or spleen, and were dispersed non-specifically in various organs. Thus, controlling the shape and mechanical properties of RBC-MPs is important for achieving the desired biodistribution. When RBC-MPs were loaded with a (TGF)-beta receptor inhibitor, RBC-MPs could treat liver fibrosis without pneumotoxicity. (C) 2017 Elsevier Ltd. All rights reserved.