4.5 Article

Detecting a Secreted Gastric Cancer Biomarker Molecule by Targeted Nanoparticles for Real-Time Diagnostics

Journal

PHARMACEUTICAL RESEARCH
Volume 29, Issue 4, Pages 983-993

Publisher

SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-011-0638-8

Keywords

fluorescent immuno-nanoparticles; gastric cancer; human alpha 1-antitrypsin-precursor; non-invasive imaging; protein immobilization

Funding

  1. NEMO consortium

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A real time detection of gastric cancer-associated biomarker molecules in the lumen of the stomach could assist in early detection of this multi-step malignancy. Employing alpha 1-antitrypsin precursor (A1AT) as a secreted biomarker model, a platform with immunoassay capabilities, comprising sensing and detecting compartments was developed. It was made of a microarray-type functionalized glass, containing a high density of amine groups. Trypsin, the capturing moiety, was immobilized to the glass surface with the aid of a PEG-based spacer mixture, identified as being crucial for both capturing and detecting properties. The detecting compartment contained near infrared fluorescently labeled nanoparticles conjugated to A1AT-specific antibodies, aimed at generating an optical signal, detectable by a conventional endoscope or a video capsule. The specific recognition reaction between the captured A1AT and the immuno-nanoparticles generated a profound fluorescence with a signal to noise ratio (SNR) of 12-32, in a biomarker-concentration dependent manner. Moreover, the optical recognition signal was intense enough to be detected by a video capsule simulator (with optical detection capabilities of a video capsule) with a SNR of 6-20. This platform could serve as a real time diagnostic kit for early detection of a secreted biomarker of gastric cancer.

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