TY - JOUR
T1 - Red blood cell-like particles with the ability to avoid lung and spleen accumulation for the treatment of liver fibrosis
AU - Hayashi, Koichiro
AU - Yamada, Shota
AU - Hayashi, Hikaru
AU - Sakamoto, Wataru
AU - Yogo, Toshinobu
N1 - Funding Information:
We are grateful to the Center for Animal Research and Education (CARE) and the Technical Center at Nagoya University. Kupffer cells (KUP5) were provided by the RIKEN BRC through the National Bio-Resource Project of the MEXT, Japan [40]. This work was supported by JSPS KAKENHI (26709050, 15K14146, 17H03403 and 15H02296). Additionally, the work was partly supported by a Health Labor Sciences Research Grant from the Ministry of Health, Labour and Welfare. The authors declare that they have no competing interests. This work was carried out by the joint research program of the Institute for Molecular Science for Sustainability, Nagoya University. This work was performed by the six universities cooperative research project, Creation of Life Innovation Materials for Interdisciplinary and International Researcher Development.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2018/2
Y1 - 2018/2
N2 - 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 (RBCs) 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)-β receptor inhibitor, RBC-MPs could treat liver fibrosis without pneumotoxicity.
AB - 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 (RBCs) 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)-β receptor inhibitor, RBC-MPs could treat liver fibrosis without pneumotoxicity.
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U2 - 10.1016/j.biomaterials.2017.11.031
DO - 10.1016/j.biomaterials.2017.11.031
M3 - Article
C2 - 29190497
AN - SCOPUS:85035024564
SN - 0142-9612
VL - 156
SP - 45
EP - 55
JO - Biomaterials
JF - Biomaterials
ER -