The discovery of the phenomena known as localized surface plasmon resonance (LSPR) has provided the basis for many research areas, ranging from materials science to biosensing. LSPR has since been viewed as a transduction platform that could yield affordable, portable devices for a multitude of applications. This review aims to outline the potential applications within developing countries and the challenges that are likely to be faced before the technology can be effectively employed.
Circulating tumor cells (CTC) are promising biomarkers for metastatic cancer detection and monitoring progression. However, detection of CTCs remains challenging due to their low frequency and heterogeneity. Herein, we report a bioinspired approach to detect individual cancer cells, based on a signal amplification cascade using a programmable DNA hybridization chain reaction (HCR) circuit. We applied this approach to detect HER2 + cancer cells using the anti-HER2 antibody (trastuzumab) coupled to initiator DNA eliciting a HCR cascade that leads to a fluorescent signal at the cell surface. At 4°C, this HCR detection scheme resulted in highly efficient, specific and sensitive signal amplification of the DNA hairpins specifically on the membrane of the HER2 + cells in a background of HER2 À cells and peripheral blood leukocytes, which remained almost nonfluorescent. The results indicate that this system offers a new strategy that may be further developed toward an in vitro diagnostic platform for the sensitive and efficient detection of CTC.[a] S.
The lack of understanding of fundamental nano-bio interactions, and difficulties in designing particles stable in complex biological environments are major limitations to their translation into biomedical clinical applications. Here we present a multi-parametric approach to fully characterize targeted nanoparticles, and emphasizes the significant effect that each detail in the synthetic process can have on downstream in vitro results. Through an iterative process, particles were designed, synthesized and tested for physico-chemical and bio-interactive properties which allowed the optimization of nanoparticle functionality. Taken together all interative steps demonstrate that we have synthesized a multifunctional gold nanoparticles that can detect ERBB2-positive breast cancer cells while showing stealth-like behavior toward ERBB2-negative cells and excellent physicochemical stability.
The main cause of cancer-related death is due to cancer cell spreading and formation of secondary tumors in distant organs, the so-called metastases. Metastatic cancer cells are detectable in the blood of cancer patients as circulating tumor cells (CTC) and may be exploited
for prognostic and monitoring purposes, including in breast cancer. Due to their very low frequency, however, their quantitative detection remains a challenge in clinical practice. Nature has developed mechanisms to amplify rare biological events or weak signals, such as intracellular signaling
pathways, cytokine networks or the coagulation cascades. At the National Center for Competence in Research (NCCR) in Bio-Inspired Materials we are coupling gold nanoparticle-based strategies with fibrinogen and DNA bio-inspired amplification cascades to develop an in vitro test to specifically
and sensitively detect CTCs in patients' blood. In this article, we describe the biological context, the concept of bio-inspired amplification, and the approaches chosen. We also discuss limitations, open questions and further potential biomedical applications of such an approach.
The Front Cover illustrates the sensitive detection of HER2+ breast cancer cells by a DNA signal amplification circuit. Circulating cancer cells (CTC), hallmarks of metastatic cancer, are difficult to detect due to infrequent occurrence. The signal of the HER2+ cell binding antibody Trastuzumab is enhanced via a DNA hybridization chain reaction. The reaction is initiated by an initiator DNA strand, coupled to the antibody. This sequence triggers the hybridization of fluorescent hairpins, forming strongly labeled DNA constructs and allowing CTC detection by flow cytometry. Artwork by Miguel Spuch‐Calvar. More information can be found in the Communication by Sarah D. Rafiee, Samet Kocabey, Michael Mayer, Jonathan List, and Curzio Rüegg..
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