Abstract |
Development of chemoresistance and rapid inactivation of gemcitabine (Gem), the standard therapy for advanced pancreatic cancer, are responsible of the major therapeutic failures. To overcome the above drawbacks we designed a novel nanomedicine strategy for Gem nanoparticle (NP) formulation based on squalene conjugation. The purpose was to investigate the antitumor efficacy of gemcitabine- squalene (SQ-Gem) NPs on chemoresistant and chemosensitive pancreatic adenocarcinoma models. Cell viability and apoptosis assays showed that SQ-Gem NPs displayed higher antiproliferative and cytotoxic effects, particularly in chemoresistant Panc1 tumor cells. In in vivo studies, compared to native Gem, SQ-Gem NPs decreased significantly the tumor growth, prevented tumor cell invasion, and prolonged the survival time of mice bearing orthotopic pancreatic tumors. These results correlate with a greater reduction of Ki-67 and induction of apoptosis. These findings demonstrate the feasibility of utilizing SQ-Gem NPs to make tumor cells more sensitive to Gem and thus provide an efficient new therapeutic alternative for pancreatic adenocarcinoma. FROM THE CLINICAL EDITOR: Pancreatic malignancies represent some of the most notoriously treatment resistant cancer varieties. This paper discusses a novel and promising nanotechnology-based treatment approach, currently at the basic science stage.
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Authors | Soukaina Réjiba, L Harivardhan Reddy, Christelle Bigand, Céline Parmentier, Patrick Couvreur, Amor Hajri |
Journal | Nanomedicine : nanotechnology, biology, and medicine
(Nanomedicine)
Vol. 7
Issue 6
Pg. 841-9
(Dec 2011)
ISSN: 1549-9642 [Electronic] United States |
PMID | 21419876
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Elsevier Inc. All rights reserved. |
Chemical References |
- Antimetabolites, Antineoplastic
- Deoxycytidine
- Squalene
- Gemcitabine
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Topics |
- Adenocarcinoma
(drug therapy, pathology)
- Animals
- Antimetabolites, Antineoplastic
(administration & dosage, chemistry, therapeutic use)
- Apoptosis
(drug effects)
- Cell Line
- Cell Line, Tumor
- Deoxycytidine
(administration & dosage, analogs & derivatives, chemistry, therapeutic use)
- Female
- Humans
- Mice
- Mice, Nude
- Nanomedicine
- Nanoparticles
(chemistry)
- Pancreas
(drug effects, pathology)
- Pancreatic Neoplasms
(drug therapy, pathology)
- Squalene
(administration & dosage, chemistry, therapeutic use)
- Gemcitabine
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