title: Fructose-Coated Nanodiamonds: Promising Platforms for Treatment of Human Breast Cancer.
abstract: Well-defined carboxyl end-functionalized glycopolymer Poly(1-O-methacryloyl-2,3:4,5-di-O-isopropylidene-β-d-fructopyranose) (Poly(1-O-MAipFru)62) has been prepared via reversible addition-fragmentation chain transfer polymerization and grafted onto the surface of amine-functionalized nanodiamonds via a simple conjugation reaction. The properties of the nanodiamond-polymer hybrid materials ND-Poly(1-O-MAFru)62 are investigated using infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, and transmission electron microscopy. The dispersibility of the nanodiamonds in aqueous solutions is significantly improved after the grafting of the glycopolymer. More interestingly, the cytotoxicity of amine-functionalized nanodiamonds is significantly decreased after decoration with the glycopolymer even at a high concentration (125 μg/mL). The nanodiamonds were loaded with doxorubicin to create a bioactive drug delivery carrier. The release of doxorubicin was faster in media of pH 5 than media of pH 7.4. The nanodiamond drug delivery systems with doxorubicin are used to treat breast cancer cells in 2D and 3D models. Although the 2D cell culture results indicate that all nanodiamonds-doxorubicin complexes are significantly less toxic than free doxorubicin, the glycopolymer-coated nanodiamonds-doxorubicin show higher cytotoxicity than free doxorubicin in the 3D spheroids after treatment for 8 days. The enhanced cytotoxicity of Poly(1-O-MAFru)62-ND-Dox in 3D spheroids may result from the sustained drug release and deep penetration of these nanocarriers, which play a role as a "Trojan Horse". The massive cell death after 8-day incubation with Poly(1-O-MAFru)62-ND-Dox demonstrates that glycopolymer-coated nanodiamonds can be promising platforms for breast cancer therapy.
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Zhao
authors.forename: Haiwang
authors.initials: H
authors.lastname: Lai
authors.forename: Hongxu
authors.initials: H
authors.lastname: Lu
authors.affiliation: Preparative Macromolecular Chemistry, Institut für Technische Chemie und Polymerchemie, Karlsruhe Institute of Technology (KIT) , Engesserstrasse 18, 76131 Karlsruhe, Germany.|Institut für Biologische Grenzflächen, Karlsruhe Institute of Technology (KIT) , Hermann-von-Helmholtz-Platz 1, 76297 Eggenstein-Leopoldshafen, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Barner-Kowollik
authors.forename: Martina H
authors.initials: MH
authors.lastname: Stenzel
authors.forename: Pu
authors.initials: P
authors.lastname: Xiao
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D005632:Fructose / Q000737:chemistry*; D006801:Humans; D058612:Nanodiamonds / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D018874:Spheroids, Cellular / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D058612:Nanodiamonds; D011108:Polymers; D005632:Fructose; D004317:Doxorubicin