Gemcitabine integrated nano-prodrug carrier system

Date
2017
Advisor
Instructor
Source Title
Bioconjugate Chemistry
Print ISSN
1043-1802
Electronic ISSN
Publisher
American Chemical Society
Volume
28
Issue
5
Pages
1491 - 1498
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
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.

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Other identifiers
Book Title
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
Citation
Published Version (Please cite this version)