title: Bringing macromolecules into cells and evading endosomes by oxidized carbon nanoparticles.
abstract: A great challenge exists in finding safe, simple, and effective delivery strategies to bring matters across cell membrane. Popular methods such as viral vectors, positively charged particles and cell penetrating peptides possess some of the following drawbacks: safety issues, lysosome trapping, limited loading capacity, and toxicity, whereas electroporation produces severe damages on both cargoes and cells. Here, we show that a serendipitously discovered, relatively nontoxic, water dispersible, stable, negatively charged, oxidized carbon nanoparticle, prepared from graphite, could deliver macromolecules into cells, without getting trapped in a lysosome. The ability of the particles to induce transient pores on lipid bilayer membranes of cell-sized liposomes was demonstrated. Delivering 12-base-long pyrrolidinyl peptide nucleic acids with d-prolyl-(1S,2S)-2-aminocyclopentanecarboxylic acid backbone (acpcPNA) complementary to the antisense strand of the NF-κB binding site in the promoter region of the Il6 gene into the macrophage cell line, RAW 264.7, by our particles resulted in an obvious accumulation of the acpcPNAs in the nucleus and decreased Il6 mRNA and IL-6 protein levels upon stimulation. We anticipate this work to be a starting point in a new drug delivery strategy, which involves the nanoparticle that can induce a transient pore on the lipid bilayer membrane.
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Sunatda
authors: S
authors: Arayachukiat
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Jiraporn
authors: J
authors: Seemork
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Porntip
authors: P
authors: Pan-In
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Kittima
authors: K
authors: Amornwachirabodee
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Naunpun
authors: N
authors: Sangphech
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Titiporn
authors: T
authors: Sansureerungsikul
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Kamonluck
authors: K
authors: Sathornsantikun
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Chotima
authors: C
authors: Vilaivan
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Kazuki
authors: K
authors: Shigyou
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Prompong
authors: P
authors: Pienpinijtham
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Tirayut
authors: T
authors: Vilaivan
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Tanapat
authors: T
authors: Palaga
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Wijit
authors: W
authors: Banlunara
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Tsutomu
authors: T
authors: Hamada
authors: †Macromolecular Science Program, Faculty of Science, Chulalongkorn University (CU), ‡Program in Petrochemistry, Faculty of Science, CU, §Department of Chemistry, Faculty of Science, CU, ∥Department of Microbiology, Faculty of Science, and Interdisciplinary Program in Medical Microbiology, CU, ⊥School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), ¶Department of Pathology, Faculty of Veterinary Science, CU, ∇Nanotec-CU Center of Excellence on Food and Agriculture, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Supason
authors: S
authors: Wanichwecharungruang
mesh_terms: D000818:Animals; D001665:Binding Sites; D002244:Carbon / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D011992:Endosomes / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry / Q000235:genetics; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry; D051379:Mice; D016328:NF-kappa B / Q000737:chemistry / Q000235:genetics; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010084:Oxidation-Reduction; D020135:Peptide Nucleic Acids / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D008051:Lipid Bilayers; D008081:Liposomes; D016328:NF-kappa B; D020135:Peptide Nucleic Acids; D002244:Carbon
keywords: PNA; antigene; cellular penetration; lipid bilayer membrane; nanoparticle; oxidized carbon particle; transient pore