title: Novel curcumin-loaded magnetic nanoparticles for pancreatic cancer treatment.
abstract: Curcumin (CUR), a naturally occurring polyphenol derived from the root of Curcuma longa, has showed potent anticancer and cancer prevention activity in a variety of cancers. However, the clinical translation of CUR 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 CUR-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 mouse model and improved the survival of mice by delaying tumor growth. The growth-inhibitory effect of MNP-CUR formulation correlated with the suppression of proliferating cell nuclear antigen (PCNA), B-cell lymphoma-extra large (Bcl-xL), induced myeloid leukemia cell differentiation protein (Mcl-1), cell surface-associated Mucin 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. In addition, the MNP-CUR formulation improved serum bioavailability of CUR in mice up to 2.5-fold as compared with free CUR. Biodistribution studies show 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.
authors.affiliation: Cancer Biology Research Center, Sanford Research/University of South Dakota, Sioux Falls, SD, USA.
authors.forename: Murali M
authors.initials: MM
authors.lastname: Yallapu
authors.forename: Mara C
authors.initials: MC
authors.lastname: Ebeling
authors.forename: Sheema
authors.initials: S
authors.lastname: Khan
authors.forename: Vasudha
authors.initials: V
authors.lastname: Sundram
authors.forename: Neeraj
authors.initials: N
authors.lastname: Chauhan
authors.forename: Brij K
authors.initials: BK
authors.lastname: Gupta
authors.forename: Susan E
authors.initials: SE
authors.lastname: Puumala
authors.forename: Meena
authors.initials: M
authors.lastname: Jaggi
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008297:Male; D051379:Mice; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D011485:Protein Binding; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001798:Blood Proteins; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D003474:Curcumin