Journal
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
Volume 62, Issue -, Pages 614-625Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.msec.2016.01.076
Keywords
Single-walled carbon nanotubes; gemcitabine; polyethylene glycol; intracellular drug delivery; A549; MIA PaCa-2
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Funding
- Shahid Beheshti University of Medical Sciences (SBUMS) [2367-16]
- Tehran University of Medical Sciences (TUMS) [783-11]
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Gemcitabine (GEM) is an anticancer agent widely used in non-small cell lung and pancreatic cancers. The clinical use of GEM has been limited by its rapid metabolism and short plasma half-life. These restrictions lead to frequent administration of high drug doses which can cause severe side effects. Therefore, new delivery strategies are needed aiming toward improved therapeutic effects. Single-walled carbon nanotubes (SWCNTs) are emerging as promising carriers for drug delivery due to their unique properties including high drug loading capacities, notable cell membrane penetrability and prolonged circulation times. In this work, pristine SWCNTs were functionalized through carboxylation, acylation, amination, PEGylation and finally GEM conjugation. The prepared SWCNT-GEM and SWCNT-PEG-GEM conjugates were characterized by FTIR, NMR, DSC and TEM to confirm the successful functionalization. The amount of GEM bound to the conjugates was 43.14% (w/w) for the SWCNT-GEM and 37.32% for the SWCNT-PEG-GEM, indicating high loading capacity. WITT assay on the human lung carcinoma cell line (A549) and the human pancreatic carcinoma cell line (MIA PaCa-2) demonstrated that the SWCNT-GEM was more cytotoxic than SWCNT-PEG-GEM and GEM. The SWCNT-PEG-GEM conjugates afford higher efficacy in suppressing tumor growth than SWCNT-GEM and GEM in B6 nude mice. The results demonstrate that the new formulation of GEM is useful strategy for improving the antitumor efficacy of GEM. (C) 2016 Elsevier B.V. All rights reserved.
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