title: Multivalent aptamer/gold nanoparticle-modified graphene oxide for mass spectrometry-based tumor tissue imaging.
abstract: The protein mucin1 (MUC1) is an attractive target for cancer biomarkers because it is overexpressed in most adenocarcinomas. In this study, we exploited a MUC1-binding aptamer (AptMUC1) as a targeting agent for nanoparticle-based imaging systems coupled with laser desorption/ionization mass spectrometry (LDI-MS). We found that AptMUC1-conjugated gold nanoparticles immobilized, through hydrophobic and π-π interactions, on graphene oxide (AptMUC1-Au NPs/GO) bound effectively to MUC1 units on tumor cell membranes. The ultrahigh density and high flexibility of AptMUC1 on the GO surface enhanced the platform's cooperative and multivalent binding affinity for MUC1 on cell membranes. After we had labeled MUC1-overexpressing MCF-7 cells (human breast adenocarcinoma cell line) with AptMUC1-Au NPs/GO, we used LDI-MS to monitor Au cluster ions ([Aun](+); n = 1-3), resulting in the detection of as few as 100 MCF-7 cells. We also employed this AptMUC1-Au NPs/GO-LDI-MS system to analyze four different MUC1 expression cell lines. In addition, the AptMUC1-Au NPs/GO platform could be used further as a labeling agent for tumor tissue imaging when coupled with LDI-MS. Thus, Apt-Au NPs/GO can function as a highly amplified signal transducer through the formation of large Au clusters ions during LDI-MS analysis.
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Rong-Cing
authors.initials: RC
authors.lastname: Huang
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Wei-Jane
authors.initials: WJ
authors.lastname: Chiu
authors.affiliation: Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan.
authors.forename: Irving
authors.initials: I
authors.lastname: Po-Jung Lai
authors.affiliation: 1] Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 20224, Taiwan [2] Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung, 20224, Taiwan [3] School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Huang
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis*; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D005260:Female; D006046:Gold / Q000737:chemistry; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D061986:MCF-7 Cells; D053768:Metal Nanoparticles / Q000737:chemistry*; D018396:Mucin-1 / Q000378:metabolism*; D011485:Protein Binding; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D046888:Tissue Array Analysis
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D006046:Gold; D006108:Graphite