Nano Archive

A new nanomedicine of gemcitabine displays enhanced anticancer activity in sensitive and resistant leukemia types

Reddy, L. Harivardhan and Dubernet, Catherine and Mouelhi, Sinda Lepetre and Marque, Pierre Emmanuel and Desmaele, Didier and Couvreur, Patrick (2007) A new nanomedicine of gemcitabine displays enhanced anticancer activity in sensitive and resistant leukemia types. JOURNAL OF CONTROLLED RELEASE, 124 (1-2). pp. 20-27.

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Gemcitabine is an anticancer nucleoside analogue active against various solid tumors. However, it possesses important drawbacks like a poor biological half-life and the induction of resistance. With the objective of overcoming the above drawbacks, we designed a new nanomedicine of gemcitabine and studied its anticancer efficacy against leukemia at preclinic. Gemcitabine has been covalently coupled with 1,1',2-tris-nor-squalenic acid to obtain the new anticancer nanomedicine 4-(N)-Tris-nor-squalenoyl-gemcitabine (SQdFdC NA). The SQdFdC NA exhibited, in comparison to gemcitabine, 3.26- and 3.22-folds higher cytotoxicity respectively, in murine resistant leukemia L1210 10K cells and in human leukemia resistant cell line CEM/ARAC8C. Following intravenous treatment of murine aggressive metastatic leukemia L1210 wt bearing mice, the SQdFdC NA caused significant increase in survival time compared to gemcitabine and also led to long-term survivals, which was not the case after gemcitabine treatment. This was attributed to significantly higher deposition of SQdFdC NA in spleen and liver (P < 0.05), the major metastatic organs. In comparison to gemcitabine, SQdFdC NA displayed greater ability to induce S-phase arrest of the cancer cells followed by increased apoptotic induction. Interestingly, like gemcitabine, SQdFdC NA didn't induce appreciable differences in blood parameters even at doses higher than those used for anticancer evaluation. The preclinical data obtained in vitro and in vivo with SQdFdC NA demonstrate that this nanomedicine represents a new therapeutic system for the effective treatment of leukemia. (c) 2007 Elsevier B.V. All rights reserved.

Item Type:Article
Uncontrolled Keywords:squalenoylation; gemcitabine; nanomedicine; leukemia; resistant cancer
Subjects:Biomedical Science > Nanomedicine
ID Code:2713
Deposited By:Farnush Anwar
Deposited On:09 Jan 2009 11:15
Last Modified:22 Jan 2009 15:15

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