Analysis of the Human Plasma Proteome Using Multi‐Nanoparticle Protein Corona for Detection of Alzheimer's Disease

Abstract

As the population affected by Alzheimer's disease (AD) grows, so does the need for a noninvasive and accurate diagnostic tool. Current research reveals that AD pathogenesis begins as early as decades before clinical symptoms. The unique properties of nanoparticles (NPs) may be exploited to develop noninvasive diagnostics for early detection of AD. After exposure of NPs to biological fluids, the NP surface is altered by an unbiased but selective and reproducible adsorption of biomolecules commonly referred to as the biomolecular corona or protein corona (PC). The discovery that the plasma proteome may be differentially altered during health and disease leads to the concept of disease‐specific PCs. Herein, the disease‐specific PCs formed around NPs in a multi‐NPs platform are employed to successfully identify subtle changes in plasma protein patterns and detect AD (>92% specificity and ≈100% sensitivity). Similar discrimination power is achieved using banked plasma samples from a cohort of patients several years prior to their diagnosis with AD. With the nanoplatform's analytic ability to analyze pathological proteomic changes into a disease‐specific identifier, this promising, noninvasive technology with implications for early detection and intervention could benefit not only patients with AD but other diseases as well.

Nanoparticle protein corona evolution: from biological impact to biomarker discovery

“…Reproduced with permission from Corbo et al 2021. 118 In other recent work, gold NPs have been used as sorbent nanomaterials for PC creation following interaction with sera of breast cancer patients and of disease-free healthy controls. Due to the NPs' specific features, such as high surface-area-tovolume ratio, colloidal stability, and the ability to conjugate with biomolecules, gold NPs' PC allowed the concentration of the low-abundance proteins, otherwise undetectable, thus helping in the identification of novel molecular targets associated to different breast cancer subtypes.…”

“…The sensitivity and specificity provided by the experiment results were identified at ≈100% and >93%, respectively, thus representing an important milestone in the field of neurodegenerative disorders diagnosis, especially if these values are compared to ones of traditional tests based on, for instance, PET imaging systems or specific biomarkers research. 118 Similarly, Digiacomo et al have used the PCs of 3 lipid NP formulations, analyzed by a supervised random forest classifier, to discriminate between oncological (breast and prostate cancer) and healthy individuals. 119 Interestingly, such a panel Fig.…”

Physiology, pathology and the biomolecular corona: the confounding factors in nanomedicine design

“…187 Nanomedicines have also been explored as Alzheimer's diagnostics. 188,189 Finally, when complexed with plasma taken from patients with different diseases, the disease-specific corona on graphene oxide sheets triggered different biological responses, changing the therapeutic impact of the graphene. Similarly, graphene oxide could be incorporated into a sensor system where the surface corona could also be used to detect specific cancers.…”

“…219 Again, combining high-throughput approaches and sophisticated data mining approaches will likely ameliorate the in vitro and in vivo correlation issue. 188,220 Overall, improving our knowledge about the range of possible biological states will help us engineer more effective nanomedicines. From this perspective, several strategies seem appropriate for improving nanomedicine performance: (I) achieve an improved understanding of how the heterogeneity of diseases and normal biological conditions influence the behavior of nanomedicines in patients and healthy individuals; (II) move from formulation-driven research to methods that evaluate formulations functionally in a relevant biological context; (III) develop biological models that reflect this context for both in vitro and in vivo testing; and, (IV) adopt a more flexible approach to nanomedicine formulation to more closely match nanomedicine characteristics to the current biological state of the recipient system.…”

Magnetic Gold Nanoparticles with Idealized Coating for Enhanced Point‐Of‐Care Sensing

“…Indeed, this concept has been exploited for plasma protein analysis via mass spectroscopy. [13][14][15] For targeted analysis however, the goal is to minimize such protein adsorption. In order to provide chemical surface anchors for the latter attachment or target-specific molecules, polymers that contain primary amines (e.g., polyethyleneimine, PEI) or carboxylate groups (e.g., polyacrylic acid) have been widely used for the modification of nanoparticles.…”