title: Structural profiling and biological performance of phospholipid-hyaluronan functionalized single-walled carbon nanotubes.
abstract: In spite of significant insolubility and toxicity, carbon nanotubes (CNTs) erupt into the biomedical research, and create an increasing interest in the field of nanomedicine. Single-walled CNTs (SWCNTs) are highly hydrophobic and have been shown to be toxic while systemically administrated. Thus, SWCNTs have to be functionalized to render water solubility and biocompatibility. Herein, we introduce a method for functionalizing SWCNT using phospholipids (PL) conjugated to hyaluronan (HA), a hydrophilic glycosaminoglycan, with known receptors on many types of cancer and immune cells. This functionalization allowed for CNT solubilization, endowed the particles with stealth properties evading the immune system, and reduced immune and mitochondrial toxicity both in vitro and in vivo. The CNT-PL-HA internalized into macrophages and showed low cytotoxicity. In addition, CNT-PL-HA did not induce an inflammatory response in macrophages as evidenced by the cytokine profiling and the use of image-based high-content analysis approach in contrast to non-modified CNTs. In addition, systemic administration of CNT-PL-HA into healthy C57BL/6 mice did not alter the total number of leukocytes nor increased liver enzyme release as opposed to CNTs. Taken together, these results suggest an immune protective mechanism by the PL-HA coating that could provide future therapeutic benefit.
authors.affiliation: Laboratory of NanoMedicine, Dept. of Cell Research & Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ram
authors.initials: R
authors.lastname: Dvash
authors.forename: Artium
authors.initials: A
authors.lastname: Khatchatouriants
authors.forename: Leonardo J
authors.initials: LJ
authors.lastname: Solmesky
authors.forename: Peter P
authors.initials: PP
authors.lastname: Wibroe
authors.forename: Miguel
authors.initials: M
authors.lastname: Weil
authors.forename: S Moein
authors.initials: SM
authors.lastname: Moghimi
authors.forename: Dan
authors.initials: D
authors.lastname: Peer
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003167:Complement Activation / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry*; D016753:Interleukin-10 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D037742:Nanotubes, Carbon; D010714:Phosphatidylethanolamines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C483858:phosphatidylethanolamine; D006820:Hyaluronic Acid
keywords: Carbon nanotubes; Cytotoxicity; High-content analysis; Hyaluronan; Immune response