Novel Curcumin Loaded Magnetic Nanoparticles for Pancreatic Cancer Treatment
Menée in vitro et à l'aide de xénogreffes, cette étude évalue l'activité antitumorale de nanoparticules magnétiques enrichies en curcumine pour le traitement d'un cancer du pancréas
Curcumin (CUR), a naturally occurring polyphenol derived from the root of Curcuma longa, has demonstrated potent anti-cancer and cancer prevention activity in a variety of cancers. However, the clinical translation of curcumin has been significantly hampered due to its extensive degradation, suboptimal pharmacokinetics and poor bioavailability. To address these clinically relevant issues, we have developed a novel curcumin loaded magnetic nanoparticle (MNP-CUR) formulation. Herein, we have evaluated the in vitro and in vivo therapeutic efficacy of this novel MNP-CUR formulation in pancreatic cancer. Human pancreatic cancer cells (HPAF-II and Panc-1) exhibited efficient internalization of the MNP-CUR formulation in a dose dependent manner. As a result, the MNP-CUR formulation effectively inhibited growth of HPAF-II and Panc-1 cells in cell proliferation and colony formation assays. The MNP-CUR formulation suppressed pancreatic tumor growth in an HPAF-II xenograft mice model and improved mice survival by delaying tumor growth. The growth inhibitory effect of MNP-CUR formulation was correlated with the suppression of PCNA, Bcl-xL, Mcl-1, MUC1, Collagen I and enhanced membrane β-catenin expression. MNP-CUR formulation did not show any sign of hemotoxicity and was stable after incubation with human serum proteins. Additionally, the MNP-CUR formulation improved serum bioavailability of curcumin in mice up to 2.5 fold as compared to free curcumin. Biodistribution studies demonstrate that a significant amount of MNP-CUR formulation was able to reach the pancreatic xenograft tumor(s) which suggests its clinical translational potential. In conclusion, this study suggests that our novel MNP-CUR formulation can be valuable for the treatment of pancreatic cancer.
http://mct.aacrjournals.org/content/early/2013/05/23/1535-7163.MCT-12-1227.abstract