Nanoparticle-Mediated Local and Remote Manipulation of Protein Aggregation

Abstract

The local heat delivered by metallic nanoparticles selectively attached to their target can be used as a molecular surgery to safely remove toxic and clogging aggregates. We apply this principle to protein aggregates, in particular to the amyloid beta protein (Abeta) involved in Alzheimer's disease (AD), a neurodegenerative disease where unnaturally folded Abeta proteins self-assemble and deposit forming amyloid fibrils and plaques. We show the possibility to remotely redissolve these deposits and to interfere with their growth, using the local heat dissipated by gold nanoparticles (AuNP) selectively attached to the aggregates and irradiated with low gigahertz electromagnetic fields. Simultaneous tagging and manipulation by AuNP of Abeta at different stages of aggregation allow both, noninvasive exploration and dissolution of molecular aggregates.

Nanoparticles as catalysts for protein fibrillation

“…Although this study found that NPs can promote fibrillation, there are ongoing efforts to use NPs to detect, prevent, and treat protein-misfolding diseases such as Alzheimer's (19)(20)(21)(22). Therefore, interpreting the results of this paper as unequivocally bad news for NPs is unwarranted.…”

Nano Gold and Biomedicine: Scientific Letter

“…38 Kogan ve ark., in vitro deneylerde altın nanopartiküllerini kullanarak Alzheimer hastalığı ile ilişkili olduğu düşünülen beta-amiloid fibrillerini ve plaklarını yok etmiştir. 39 Çalışmada altın nanopartikülleri beta-amiloid fibril grubuna iliştirilerek 48 saatlik inkübasyon süresinin ardından sekiz saat zayıf mikrodalga alan içerisinde tutulmuştur. Işın-lama sonrası fibrillerin büyük oranda yok olduğu gözlemlenmiştir.…”

“…Araştır-macılar benzer yaklaşımdan hareketle, protein agregasyonun yol açtığı Parkinson ve Huntington gibi diğer nörodejeneratif hastalıkların tedavisi üzerine çalışmaktadır. 39 Oküler hastalıkların tedavisinde de kullanılan altın nanopartiküller özellikle retina altı bölgelere terapötik ajanların taşınmasında tercih edilmektedir. Oküler anjiyogenez, proliferatif diyabetik retinopati ve n ne eo ov va as sk kü ül le er r m ma ak ku ul lo op pa at ti i g gi ib bi i h ha as st ta al lı ık kl la ar r g gö ör rm me e d du uy yu us su un na a z za ar ra ar r v ve er rm me ek kt te ed di ir r. .…”

The Reactivity of Colloidal Inorganic Nanoparticles

“…In biomedicine, INPs have to be functionalized in order to selectively interact with biological targets. For this purpose, they are usually coated with biological molecules such as antibodies (Wang et al, 2002;El-Sayed et al, 2005), aptamers (Farokhzad et al, 2006), peptides (Kogan et al, 2006;Bastús et al, 2009), and oligonucleotides (Rosi et al, 2006). Some relevant examples are the functionalization of INPs with uptake ligands that specifically bind to receptors of the cell membrane (ex.…”