Novel Curcumin-Loaded Magnetic Nanoparticles for Pancreatic Cancer Treatment

Abstract

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.

Effects of Micro-environmental pH of Liposome on Chemical Stability of Loaded Drug

“…It is well known that curcumin is a lipophilic molecule and has been extensively used in food, medicines, and cosmetics due to its various bioactivities [17][18][19][20][21]. However, its delivery is highly limited by its insolubility and instability in biological fluids [22][23][24][25]. So far, it is yet to fulfill its clinical promise in part due to pH-mediated instability [26].…”

Nanoformulations for Therapy of Pancreatic and Liver Cancers

“…Gold nanoshells in silica epilayers doped with iron oxide and the NIR dye indocyanine green (ICG) can achieve both NIR and magnetic resonance contrasts in tumors [27]. Additionally, the presence of a NIR agent augments photothermal ablation of pancreatic tumors [28]. Despite this, poor cellular uptake, low serum bioavailability and longitudinal imaging of these NPs is yet to be resolved.…”

“…To address this, recently triplecrown magnetic NPs (MNPs) have been reported. These MNP nanoformulation contain Fe 3+ and Fe 2+ salts, cyclodextrin, Pluronic F-127, and curcumin, and are efficiently internalized in a dose-dependent manner in vivo and in vitro by HPAF-II and Panc-1 tumors cells [28]. Treatment with MNPs result in tumor growth suppression by 71% in a HPAF-II xenograft mouse model.…”

Polymeric micelle-coated mesoporous silica nanoparticle for enhanced fluorescent imaging and pH-responsive drug delivery

“…Curcumin, a naturally occurring polyphenol and an active ingredient isolated from the root of Curcuma longa, was used as fluorescent anticancer drug model in the study. It can kill a variety of cancer cells, and has cancer prevention in many kinds of cancers [25]. However, curcumin has poor water solubility.…”