title: The hemocompatibility of oxidized diamond nanocrystals for biomedical applications.
abstract: Low-dimensional carbon-based nanomaterials have recently received enormous attention for biomedical applications. However, increasing evidence indicates that they are cytotoxic and can cause inflammatory responses in the body. Here, we show that monocrystalline nanodiamonds (NDs) synthesized by high-pressure-high-temperature (HPHT) methods and purified by air oxidation and strong oxidative acid treatments have excellent hemocompatibility with negligible hemolytic and thrombogenic activities. Cell viability assays with human primary endothelial cells suggested that the oxidized HPHT-NDs (dimensions of 35-500 nm) are non-cytotoxic. No significant elevation of the inflammatory cytokine levels of IL-1β and IL-6 was detected in mice after intravenous injection of the nanocrystals in vivo. Using a hindlimb-ischemia mouse model, we demonstrated that 35-nm NDs after covalent conjugation with polyarginine are useful as a drug delivery vehicle of heparin for prolonged anticoagulation treatment. The present study lays a solid foundation for further therapeutic applications of NDs in biomedicine.
authors.affiliation: 1] Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 106, Taiwan [2].
authors.forename: Hung-Cheng
authors.initials: HC
authors.lastname: Li
authors.forename: Feng-Jen
authors.initials: FJ
authors.lastname: Hsieh
authors.forename: Ching-Pin
authors.initials: CP
authors.lastname: Chen
authors.forename: Ming-Yao
authors.initials: MY
authors.lastname: Chang
authors.forename: Patrick C H
authors.initials: PC
authors.lastname: Hsieh
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Chen
authors.forename: Shain-Un
authors.initials: SU
authors.lastname: Hung
authors.forename: Che-Chih
authors.initials: CC
authors.lastname: Wu
authors.forename: Huan-Cheng
authors.initials: HC
authors.lastname: Chang
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry; D002470:Cell Survival; D018130:Diamond / Q000737:chemistry*; D006461:Hemolysis; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008422:Materials Testing; D051379:Mice; D058726:Nanoconjugates / Q000737:chemistry / Q000627:therapeutic use / Q000648:ultrastructure; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010314:Partial Thromboplastin Time; D010316:Particle Size
chemical_list: D000925:Anticoagulants; D001672:Biocompatible Materials; D058726:Nanoconjugates; D018130:Diamond; D006493:Heparin