title: Curcumin in VIP-targeted sterically stabilized phospholipid nanomicelles: a novel therapeutic approach for breast cancer and breast cancer stem cells.
abstract: Breast cancer is a leading cause of cancer deaths among women in the US, with 40 % chance of relapse after treatment. Recent studies outline the role of cancer stem cells (CSCs) in tumor initiation, propagation, and regeneration of cancer. Moreover, it has been established that breast CSCs reside in a quiescent state that makes them more resistant to conventional cancer therapies than bulk cancer cells resulting in tumor relapse. In this study, we establish that CSCs are associated with the overexpression of vasoactive intestinal peptide (VIP) receptors which can be used to actively target these cells. We investigated the potential of using a novel curcumin nanomedicine (C-SSM) surface conjugated with VIP to target and hinder breast cancer with CSCs. Here, we formulated, characterized, and evaluated the feasibility of C-SSM nanomedicine in vitro. We investigated the cytotoxicity of C-SSM on breast cancer cells and CSCs by tumorsphere formation assay. Our results suggest that curcumin can be encapsulated in SSM up to 200 μg/ml with 1 mM lipid concentration. C-SSM nanomedicine is easy to prepare and maintains its original physicochemical properties after lyophilization, with an IC50 that is significantly improved from that of free curcumin (14.2±1.2 vs. 26.1±3.0 μM). Furthermore, C-SSM-VIP resulted in up to 20 % inhibition of tumorsphere formation at a dose of 5 μM. To this end, our findings demonstrate the feasibility of employing our actively targeted nanomedicine as a potential therapy for CSCs-enriched breast cancer.
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Ece
authors.initials: E
authors.lastname: Gülçür
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Mentor
authors.initials: M
authors.lastname: Thaqi
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Fatima
authors.initials: F
authors.lastname: Khaja
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Antonina
authors.initials: A
authors.lastname: Kuzmis
authors.affiliation: Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, USA; Department of Biopharmaceutical Sciences (M/C 865) College of Pharmacy, University of Illinois at Chicago, 833 South Wood St., Chicago, IL 60612-7231, USA.
authors.forename: Hayat
authors.initials: H
authors.lastname: Önyüksel
keywords: Breast cancer stem cells; Curcumin; Nanoparticles; Sterically stabilized phospholipid micelles; Targeted drug delivery; Vasoactive intestinal peptide