Decentralized nanoparticle protein corona analysis may misconduct biomarker discovery

Protein/biomolecular corona (PC) is a layer of biomolecules (mainly proteins) that forms around the nanoparticles (NPs) after exposure to biological environments (e.g., blood). The dynamic nature of the PC formation allows enrichment of specific proteins particularly low abundance proteins and enables capturing disease-specific proteins on the surface of the NPs for biomarker discovery. However, identification of crucial proteins with high diagnostic values heavily depends on liquid chromatography mass spectrometry (LC-MS/MS) approach due to its sensitivity and specificity. Despite the widespread use of MS, there exist potential pitfalls in NPs’ PC analysis that may lead to misconduct in biomarker discovery studies. This opinion considers these pitfalls, providing insights into the challenges and strategies to mitigate misconduct in biomarker discovery using mass spectrometry techniques.