title: Nanoparticle-linked antagonist for leptin signaling inhibition in breast cancer.
abstract: OBJECTIVE
  To develop a leptin peptide receptor antagonist linked to nanoparticles and determine its effect on viability of breast cancer cells.
  
  
  METHODS
  The leptin antagonist, LPrA2, was coupledviaEDAC [1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide] to iron oxide nanoparticles (IONP-LPrA2) to increase its efficacy. IONP-LPrA2 conjugation was confirmed by Western blot and nanoparticle tracking analysis. Human triple negative breast cancer (TNBC) MDA-MB-231, HCC1806 and estrogen receptor positive (ER+) MCF-7 cells were analyzed for the expression of the leptin receptor, Ob-R. The effects of leptin and antagonist on levels of leptin-induced STAT3 phosphorylation and cyclin D1, cell cycle progression, cell proliferation, and tumorsphere formation in breast cancer cells were determined. Doses of the chemotherapeutics [cisplatin (Cis), cyclophosphamide (CTX), doxorubicin (Dox) and paclitaxel (PTX)] to effectively reduce cell viability were calculated. The effects of combination treatments of IONP-LPrA2 and chemotherapeutics on cell viability were determined.
  
  
  RESULTS
  Western blot analysis of coupling reaction products identified IONP-LPrA2 at approximately 100 kD. IONP-LPrA2 significantly decreased leptin-induced pSTAT3 levels in HCC1806 cells and drastically decreased cyclin D1 levels in all cell lines. IONP-LPrA2 significantly reduced leptin-induced S phase progression and cell proliferation in all breast cancer cell lines and the formation of tumorspheres in MDA-MB-231 cells. Also, IONP-LPrA2 showed an additive effect on the reduction of breast cancer cell survival with chemotherapeutics. Cis plus IONP-LPrA2 produced a significant reduction in the survival of MDA-MB-231 and HCC1806 cells. CTX plus IONP-LPrA2 caused a significant decrease in the survival of MDA-MB-231 cells. Dox plus IONP-LPrA2 caused a marked reduction in the survival of HCC1806 cells. Although, PTX plus IONP-LPrA2 did not have a major effect on the viability of the breast cancer cells when compared to PTX alone.
  
  
  CONCLUSIONS
  Present data indicate that IONP-LPrA2 may be a useful adjuvant for chemotherapeutic treatment of breast cancer, particularly for TNBC which lacks targeted therapeutic options.
authors.affiliation: Tia Harmon, Adriana Harbuzariu, Viola Lanier, Crystal C Lipsey, Ward Kirlin, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, United States.
authors.forename: Tia
authors.initials: T
authors.lastname: Harmon
authors.affiliation: Tia Harmon, Adriana Harbuzariu, Viola Lanier, Crystal C Lipsey, Ward Kirlin, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, United States.
authors.forename: Adriana
authors.initials: A
authors.lastname: Harbuzariu
authors.affiliation: Tia Harmon, Adriana Harbuzariu, Viola Lanier, Crystal C Lipsey, Ward Kirlin, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, United States.
authors.forename: Viola
authors.initials: V
authors.lastname: Lanier
authors.affiliation: Tia Harmon, Adriana Harbuzariu, Viola Lanier, Crystal C Lipsey, Ward Kirlin, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, United States.
authors.forename: Crystal C
authors.initials: CC
authors.lastname: Lipsey
authors.affiliation: Tia Harmon, Adriana Harbuzariu, Viola Lanier, Crystal C Lipsey, Ward Kirlin, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, United States.
authors.forename: Ward
authors.initials: W
authors.lastname: Kirlin
authors.affiliation: Tia Harmon, Adriana Harbuzariu, Viola Lanier, Crystal C Lipsey, Ward Kirlin, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, United States.
authors.forename: Lily
authors.initials: L
authors.lastname: Yang
authors.affiliation: Tia Harmon, Adriana Harbuzariu, Viola Lanier, Crystal C Lipsey, Ward Kirlin, Ruben R Gonzalez-Perez, Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, United States.
authors.forename: Ruben R
authors.initials: RR
authors.lastname: Gonzalez-Perez
keywords: Chemotherapy adjuvant; Iron oxide nanoparticles; Leptin; Leptin peptide receptor antagonist 2; Obesity; Triple negative breast cancer