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.

Biosensors based on graphene oxide and its biomedical application

“…Besides, the GO dispersed in aqueous solution was also used for LDI-MS analysis of other small molecules, environmental pollutant, and even polymer [68][69][70]. Moreover, there have been recent attempts to develop multifunctional matrix by adding other materials such as Fe 3 O 4 , TiO 2 , CoNP, and AuNP to the GO scaffold [71,74]. These GO-based nanocomposite matrix could provide additional functions including target enrichment for determination of the low abundant analytes and functionalization of targeting agent and signal transducer for tumor tissue imaging.…”

“…LDI-MS-based imaging using GO/MWNT film revealed the reliable lipid distribution in mouse brain tissue of which thin section was just placed on the film without requiring additional matrix treatment. More recently, Huang et al reported multivalent aptamer/AuNP modified GO for imaging of breast tumor tissue based on LDI-MS [74]. The authors exploited aptamer as a targeting probe for protein mucin 1 overexpressed on MCF-7 cells and GO as a template for the formation of gold cluster and matrix for absorbing the laser energy.…”

Satellite-like Gold Nanocomposites for Targeted Mass Spectrometry Imaging of Tumor Tissues

“…The self-assembled nanosatellite AS1411-Au NPs/Au@PC NP possess high specificity toward the target nucleolin overexpressed tumor cells. Compared to our previous aptamer-Au NPs modified graphene oxide nanocomposite for protein targeting 69 , the preparation of self-assembled and label-free AS1411-Au NPs/Au@PC NP is relatively straightforward. Moreover, the AS1411-Au NPs/Au@PC NP provide a huge signal of [Au n ] + cluster ions in the LDI-MS analysis.…”

A signal amplification electrochemical aptasensor for the detection of breast cancer cell via free-running DNA walker

“…The principle of our proposed signal amplification DNA walking machine is depicted in Fig.1. As shown in Fig.1, in the presence of MCF-7 cell, the DNA walker is released from the duplex of DNA walker/Ap because of specific recognition and high affinity binding between MUC1 mucin, exposed on the surface of MCF-7 cell, and MUC1 aptamer (Huang et al, 2015;Yang et al, 2015;Hua et al, 2013) Fig. S1 A), yet experiences a substantial decrease after cleavage event (curve c in Fig.…”