Peptide-based biosensing approaches for targeting breast cancer-derived exosomes

In disease diagnostics, the quest for non-invasive biomarkers has long been a holy grail. Among the emerging candidates, exosomes—tiny nanovesicles found in various bodily fluids—have captured researchers’ attention for their potential role in detecting diseases like cancer. However, harnessing the power of exosomes for diagnostics has proven challenging due to their complex nature and the need for precise molecular characterization.

In a new study, researchers at the State University of São Paulo (UNESP) and the Universitat Autònoma de Barcelona have embarked on a journey to overcome these hurdles by exploring the use of peptides as alternatives to antibodies for exosome binding. Peptides, short chains of amino acids, offer several advantages, including cost-effectiveness and stability, making them attractive candidates for diagnostic applications.

Using cutting-edge phage display technology, the researchers set out to select peptides with high specificity for target molecules present on exosomes. After rigorous screening, a selected peptide was put to the test, evaluated for its ability to selectively bind exosomes derived from breast cancer cells.

Magneto-actuated immunoassay for the detection of exosomes derived from breast cancer cell lines MCF-7, MDA-MB231, SKBr3, and fibroblast cell line MRC-5 as non-tumorigenic negative control. (A) Schematic outline of the approach, involving the covalent immobilization of anti-CD63 on magnetic particles, followed by labeling with biotin-C3 peptide and streptavidin-polyHRP, and colorimetric reaction with TMB. (B) Calibration plots at 450 nm at exosome concentration ranging from 150 to 4.8 × 106 exosomes μL−1, fitted using a non-linear regression (four-parameter logistic equation) (n = 3).

The results were promising: proteomic analysis identified 38 protein candidates targeted by the peptide on exosome membranes. Through advanced techniques like flow cytometry and magneto-actuated immunoassays, the researchers successfully demonstrated the peptide’s binding affinity to breast cancer-derived exosomes.

But the innovation didn’t stop there. Researchers also explored the potential of an electrochemical biosensor for detecting and quantifying breast cancer-derived exosomes—a move that could revolutionize cancer diagnostics.

In testing, the peptide exhibited effective binding to exosomes from aggressive cancer cell lines, offering hope for improved specificity and recovery rates in diagnostic assays. This breakthrough research opens doors to the development of rapid, accessible diagnostic tools for breast cancer, particularly in low-resource healthcare settings where such innovations are desperately needed.

da Fonseca Alves R, Pallarès-Rusiñol A, Rossi R, Martí M, Vaz ER, de Araújo TG, Sotomayor MDPT, Pividori MI. (2024) Peptide-based biosensing approaches for targeting breast cancer-derived exosomes. Biosens Bioelectron 255:116211. [article]

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