Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection

Abstract

SummaryProteases, 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.

In vitro methods for testing antiviral drugs

“…Fluorogenic substrates have been used to determine the activity of coronavirus proteases and screen inhibitors (Kuo et al, 2004;Lee et al, 2014;Park et al, 2017;Song et al, 2014;Tomar et al, 2015;Wang et al, 2016;Yang et al, 2005;Zhao et al, 2008). Some recently described arrangements employ nanoparticles (Feltrup and Singh, 2012;Khalilzadeh et al, 2016;Udukala et al, 2016;Wang et al, 2014;Zeng et al, 2015) or quantum dot bioconjugates (Lee and Kim, 2015;Li et al, 2014;Medintz et al, 2006) with immobilized fluorescently or luminescently labeled peptide substrates. Alternatively, cleavage products may be monitored by analysis of proteolytic products by mass spectrometric methods (Hu et al, 2015;Joshi et al, 2017;Lathia et al, 2011;Rumlová et al, 2003), analytical HPLC (Teruya et al, 2016), or electrochemical methods based on the difference in penetration of substrate and cleavage products through the membrane of a polyionselective sensor (Gemene and Meyerhoff, 2011;Han et al, 1996).…”

Synergy of Iron Chelators and Therapeutic Peptide Sequences Delivered via a Magnetic Nanocarrier

“…The peptide sequence PLFAERL D [KLAKLAKKLAKLAK]CGKRK was synthesized by solid phase peptide synthesis, as previously described [ 18 , 19 , 25 ]. In short, the peptide was synthesized on a lysine preloaded trityl resin by means of solid-phase supported synthesis from the C-terminus to the N-terminus.…”

“…By conjugating PLFAERL D [KLAKLAK] 2 CGKRK to the surface of an iron/iron oxide (Fe/Fe 3 O 4 ) nanoparticle [ 15 , 16 , 17 , 18 , 19 ] we can actively target tumors. Iron is an important element for multiple cellular processes, as for instance proliferation, and DNA synthesis [ 20 , 21 ].…”

Magnetic Nanomaterials for Magnetically-Aided Drug Delivery and Hyperthermia

“…Bossmann and co-workers have developed fluorescence-based nanobiosensors for the detection of solid tumors in liquid biopsies and protease detection in blood [18,22,[76][77][78]. These nanobiosensors feature Fe/Fe 3 O 4 core/shell nanoparticles, which were synthesized by using thermal decomposition of Fe(CO) 5 in the presence of oleylamine and hexadecylammonium chloride (HADxHCl) using 1-octadecene (ODE) as solvent [79].…”