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      Gemcitabine integrated nano-prodrug carrier system

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      Author(s)
      Hamsici, S.
      Ekiz, M. S.
      Ciftci, G. C.
      Tekinay, A. B.
      Güler, Mustafa O.
      Date
      2017
      Source Title
      Bioconjugate Chemistry
      Print ISSN
      1043-1802
      Publisher
      American Chemical Society
      Volume
      28
      Issue
      5
      Pages
      1491 - 1498
      Language
      English
      Type
      Article
      Item Usage Stats
      220
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      390
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      Abstract
      Peptide nanomaterials have received a great deal of interest in drug-delivery applications due to their biodegradability, biocompatibility, suitability for large-scale synthesis, high drug-loading capacities, targeting ability, and ordered structural organization. The covalent conjugation of drugs to peptide backbones results in prolonged circulation time and improved stability of drugs. Therapeutic efficacy of gemcitabine, which is used for breast cancer treatment, is severely compromised due to its rapid plasma degradation. Its hydrophilic nature poses a challenge for both its efficient encapsulation into nanocarrier systems and its sustained release property. Here, we designed a new peptide prodrug molecule for the anticancer drug gemcitabine, which was covalently conjugated to the C-terminal of 9-fluorenylmethoxy carbonyl (Fmoc)-protected glycine. The prodrug was further integrated into peptide nanocarrier system through noncovalent interactions. A pair of oppositely charged amyloid-inspired peptides (Fmoc-AIPs) were exploited as components of the drug-carrier system and self-assembled into one-dimensional nanofibers at physiological conditions. The gemcitabine integrated nanoprodrug carrier system exhibited slow release and reduced the cellular viability of 4T1 breast cancer cell line in a time- and concentration-dependent manner.
      Keywords
      9 fluorenylmethoxy carbonyl protected glycine
      Amino acid
      Gemcitabine
      Glycine derivative
      Nanocarrier
      Unclassified drug
      Antineoplastic antimetabolite
      Drug carrier
      Nanomaterial
      Antineoplastic activity
      Breast cancer cell line
      Cell viability
      Controlled study
      Cytotoxicity
      Drug conjugation
      Drug delivery system
      Drug efficacy
      Drug structure
      Sustained drug release
      Analogs and derivatives
      Breast neoplasms
      Cell proliferation
      Cell survival
      Chemistry
      Drug effects
      Pathology
      Tumor cell culture
      Amyloid
      Antimetabolites, antineoplastic
      Deoxycytidine
      Female
      Humans
      Nanofibers
      Nanostructures
      Prodrugs
      Permalink
      http://hdl.handle.net/11693/37309
      Published Version (Please cite this version)
      http://dx.doi.org/10.1021/acs.bioconjchem.7b00155
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      • Institute of Materials Science and Nanotechnology (UNAM) 2260
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