title: Supramolecular Detoxification of Neurotoxic Nanofibrils of Small Molecules via Morphological Switch.
abstract: Insoluble amyloid plagues are likely cytoprotective, but the cellular mechanism remains less known. To model β-amyloid we use a small peptide derivative to generate cytotoxic nanofibrils that cause the death of model neuron cells (i.e., PC12). The use of supramolecular interaction effectively converts the nanofibrils to nanoparticles that are innocuous to cells. This approach also removes the cytotoxicity of the fibrils to other mammalian cells (e.g., HeLa). Preliminary mechanistic study reveals that, in contrast to the fibrils, the particles promote the expression of TNFR2, a cell survival signal, and decrease the expression of TNFR1 and DR5, two extrinsic cell death receptors. As the first use of ligand-receptor interaction to abrogate the cytotoxicity of nanoscale assemblies of small molecules, this work illustrates an effective way to use supramolecular interaction to control the morphology of supramolecular assemblies for modulating their biological activity.
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, MS 015, Waltham, Massachusetts 02453, United States.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, MS 015, Waltham, Massachusetts 02453, United States.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, MS 015, Waltham, Massachusetts 02453, United States.
authors.forename: Dan
authors.initials: D
authors.lastname: Yuan
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, MS 015, Waltham, Massachusetts 02453, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Haburcak
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, MS 015, Waltham, Massachusetts 02453, United States.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.affiliation: Department of Chemistry, Brandeis University , 415 South Street, MS 015, Waltham, Massachusetts 02453, United States.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D049329:Nanostructures / Q000737:chemistry* / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D009498:Neurotoxins / Q000737:chemistry* / Q000633:toxicity*; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D014640:Vancomycin / Q000737:chemistry
chemical_list: D008024:Ligands; D009498:Neurotoxins; D009842:Oligopeptides; D014640:Vancomycin