title: Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection.
abstract: Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis.
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Dinusha N
authors.initials: DN
authors.lastname: Udukala
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Hongwang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Sebastian O
authors.initials: SO
authors.lastname: Wendel
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Aruni P
authors.initials: AP
authors.lastname: Malalasekera
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Thilani N
authors.initials: TN
authors.lastname: Samarakoon
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Asanka S
authors.initials: AS
authors.lastname: Yapa
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Gayani
authors.initials: G
authors.lastname: Abayaweera
authors.affiliation: Kansas State University, Department of Anatomy & Physiology, 228 Coles Hall, Manhattan, KS, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Basel
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Maynez
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Raquel
authors.initials: R
authors.lastname: Ortega
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Yubisela
authors.initials: Y
authors.lastname: Toledo
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Leonie
authors.initials: L
authors.lastname: Bossmann
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Colette
authors.initials: C
authors.lastname: Robinson
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Katharine E
authors.initials: KE
authors.lastname: Janik
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Olga B
authors.initials: OB
authors.lastname: Koper
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, USA.
authors.forename: Massoud
authors.initials: M
authors.lastname: Motamedi
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Higgins
authors.affiliation: Kansas State University, Department of Statistics, 101 Dickens Hall, Manhattan, KS, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Gadbury
authors.affiliation: The First Affiliated Hospital of Kunming Medical University, Department of Nuclear Medicine, 295 Xichang Road, Kunming, Yunnan, PR China.
authors.forename: Gaohong
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Kansas State University, Department of Anatomy & Physiology, 228 Coles Hall, Manhattan, KS, USA.
authors.forename: Deryl L
authors.initials: DL
authors.lastname: Troyer
authors.affiliation: Kansas State University, Department of Chemistry, 213 CBC Building, Manhattan, KS, USA.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Bossmann
keywords: biophotonics; breast cancer; iron/iron oxide nanoparticle; liquid biopsy; nanodiagnostics detection; nanomedicine; sub-femtomolar limit of detection