Red blood cell-like particles with the ability to avoid lung and spleen accumulation for the treatment of liver fibrosis

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.