CINMAB · Chiral Plasmons in Protein-Nanoparticle Hybrid Materials for Application as Biosensors

Chiral Plasmons in Protein-Nanoparticle Hybrid Materials for Application as Biosensors

Problem being addressed: Early diagnosis and therapy of neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s disease (PD) is a major challenge for the scientific community. While the mechanisms leading to these class of diseases is not fully understood, a common hallmark is a conformational change of native proteins leading to the aggregation and formation of insoluble amyloid fibrils. Various difficulties associated with the detection of protein aggregates, including (i) the insoluble nature of aggregates, (ii) differences in conformational and misfolding patterns depending on the type of protein, and (iii) the diverse nature of aggregates, ranging from 2D crystals to amorphous structures and fibrils making the problem a challenging one. Plasmonic nanoparticles (NPs) have recently attracted large attention in the biomedical field. Hence, the major aim of the project was to develop a new diagnostic platform for the detection of neurodegenerative diseases using plasmonic NPs. Impact on society: Untreatable conditions arising from age-related neurodegenerative diseases are matter of huge concern. The increasing socioeconomic impact of these diseases has boosted research interests on the fundamental aspects of these disorders. The early diagnosis as well as treatment of these diseases is of prime importance in tackling these social challenges. Currently, almost 16% of the European population is over the age of 65 years, and this figure is expected to reach 25% by 2030. Over 6.3 million people around the world are affected by PD and related disorders among which 1.2 million are in Europe. Approximately €130 billion per annum is spent on people with dementia across Europe, highlighting the socioeconomic impact of such diseases. Therefore, these diseases are considered as one of the leading medical and societal challenges faced by the European society, demanding early diagnosis and therapy. Considering the relevance of this topic, the project was focused on the use of plasmonic NPs for the detection of amyloid fibrils in PD and prion diseases. Overall objective: The major objective of the project was to develop a plasmonic platform for the detection of neurodegenerative diseases. The identification of protein fibrils, which are the hallmark of these diseases, is pivotal in disease diagnosis and development of therapeutic strategies. Our objective was to develop a methodology for the specific detection of amyloid fibrils using chiral effects in plasmonic NPs. The formation of amyloid fibrils based on α-synuclein (aggregation of which causes PD) was probed using gold nanorods (Au NRs). Au NRs showed no apparent interaction with monomeric proteins but effective adsorption onto fibril structures via noncovalent interactions. The technique was successfully applied for the detection of fibrils in PD-affected human brain samples.

Data: CORDIS, © European Union