Fe–Au Nanoparticle‐Coupling for Ultrasensitive Detections of Circulating Tumor DNA

Abstract

Effectiveness of cancer therapy relies heavily on the efficient early diagnosis. Circulating tumor DNA (ctDNA) detection is one of the most clinically meaningful liquid biopsy approaches for the noninvasive cancer early diagnosis, which, unfortunately, cannot be applied as a routine diagnostic tool till a number of obstacles, for example, unsatisfactory specificity and sensitivity, and extremely high costs, are overcome. Here, the first paradigm of nanomaterial's application in the extremely specific, ultrasensitive, and yet economical ctDNA detections is reported based on a facile nanoparticle-coupling strategy without amplification, with which polymerase chain reaction (PCR)-introduced bias and other shortcomings are successfully circumvented. Aiming at seven Kirsten rat sarcoma-2 virus (KRAS) point mutations, the present strategy exhibits high specificity and an ultrahigh sensitivity of detecting as low as 0.1 pg mL of KRAS point mutation without prior PCR amplification. Discriminating KRAS gene mutations in lung adenocarcinoma patients at an extremely low detection limit equivalent to 0.12% mutation relative to wild-type gene is successful. It is envisioned that this nanoparticle-coupling approach could be routinely applied clinically for ultra-early diagnosis and monitoring of diverse malignant tumors, thus facilitating the fight against cancer.

Superparamagnetic nanoarchitectures for disease-specific biomarker detection

“…94,95 Au-containing MNPs (mostly iron oxide based) (Au@MNPs) have attracted particular interest in the electroanalytical chemistry for bioseparation, the fabrication of immunoassays, and the development of optical and electrochemical sensors due to the superparamagnetic properties of magnetic materials and the biofavorable (i.e., optical and electrical) behavior of Au. 96,97 Different synthetic approaches have been reported for monodispersed Au-FexOy nanohybrids with diverse morphologies such as core/satellite, core/shell, multilayer, Au-coated iron oxide, and flower-like structures (Fig. 3).…”

A materials-science perspective on tackling COVID-19

“…Improving the sensitivity, specificity and simplicity of virus-detection methods is important to ensure accurate and rapid testing of samples. For example, an Fe–Au nanoparticle-coupling approach, combining PCR amplification with the quantitative measurement of Au nanoparticles using inductively coupled plasma mass spectrometry 129 , which was originally developed for the detection of circulating tumour DNA, could also be applied for the sensitive and specific detection of SARS-CoV-2 RNA. Microarrays, which have been developed for the precise control and manipulation of fluids, combine sample preparation, reaction, separation and detection on one chip of a few square centimetres 130 , and could be used in combination with surface-enhanced Raman spectroscopy for rapid virus detection using nanoparticle aggregates or arrays that can generate surface-enhanced Raman spectroscopy signals 131 , 132 .…”

Gold nanomaterials in the management of lung cancer

“…As an example, Su and co-workers [52] developed hierarchical, flower-like gold nanostructures assembled with DNA probes for subsequent hybridisation detection of miRNA-21 resulting in sensitivity as low as 1 fM. Gold nanostructures have also been used to improve the detection of circulating tumour DNA [53], long-noncoding RNAs [54] and other types of microRNAs [55][56][57][58] associated with LC.…”