title: Size-dependent interaction of cells and hemoglobin-albumin based oxygen carriers prepared using the SPG membrane emulsification technique.
abstract: Hemoglobin-based oxygen carriers (HBOCs) of various sizes have been developed so far, but their optimum size has not been clarified yet. Here, we examined the effect of HBOCs size on their interaction with cells using Shirasu porous glass (SPG) membrane emulsification technique, which enables precise tuning of particle size. Microspheres composed of bovine hemoglobin (bHb) and bovine serum albumin (BSA) was fabricated with the average diameters of 1.2-18.3 μm and the coefficient of variation of below 13%. Cellular uptake of the microspheres by RAW264.7 was observed at a diameter below 5 μm; however, uptake of the microspheres by HepG2 and HUVEC were not observed at any diameter. No enhancement of the generation of reactive oxygen species in the cytoplasm was detected at diameters above 9.8 μm in the three cell lines, due to their low cellular uptake. In addition, cytotoxicity of the microspheres decreased with increasing microsphere diameter in the three cell lines and microspheres of 18.3 μm showed good cellular compatibility regardless of the oxyhemoglobin percentage. Since cytotoxicity is a crucial factor in their applications, our systemic investigation would provide a new insight into the design of HBOCs.
authors.affiliation: Dept. of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo , 113-8656, Japan.
authors.forename: Yao-Tong
authors.initials: YT
authors.lastname: Lai
authors.affiliation: Center for Disease Biology and Integrative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo , 113-0033, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Dept. of Environmental Chemistry and Chemical Engineering, Kogakuin University, 2665-1, Nakano-machi, Hachioji-shi, Tokyo , 192-0015, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Akamatsu
authors.affiliation: Dept. of Environmental Chemistry and Chemical Engineering, Kogakuin University, 2665-1, Nakano-machi, Hachioji-shi, Tokyo , 192-0015, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Nakao
authors.affiliation: Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo , 153-8505, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sakai
authors.affiliation: Dept. of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo , 113-8656, Japan.|Center for Disease Biology and Integrative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo , 113-0033, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Ito
mesh_terms: D000818:Animals; D001709:Biotechnology; D002417:Cattle; D048429:Cell Size; D004655:Emulsions / Q000737:chemistry*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D005898:Glass; D006454:Hemoglobins / Q000378:metabolism*; D008567:Membranes, Artificial; D008863:Microspheres; D010316:Particle Size; D016062:Porosity; D012710:Serum Albumin, Bovine / Q000378:metabolism*
chemical_list: D004655:Emulsions; D006454:Hemoglobins; D008567:Membranes, Artificial; D012710:Serum Albumin, Bovine
keywords: Shirasu porous glass membrane; albumin; cellular uptake; hemoglobin; membrane emulsification