Nanomedicines for Alzheimer's disease: Therapies based on pathological mechanisms

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Because of the complex pathogenesis of AD and the unique location of AD lesions, effective clinical treatment strategies for this disease remain elusive. However, the development of nanotechnology has allowed a new era of AD treatment to emerge. AD nanomedicines are products of interdisciplinary research that enable high precision and targeted delivery. Additionally, they can specifically regulate various pathogenic factors. This review focuses on nanomedicines based on the pathological mechanisms of AD that can target AD lesions. We also discuss the precise regulatory effects of nanomedicines (including the nanomaterials themselves) on pathogenic proteins, neuroinflammatory molecules, and other pathogenic factors. We summarize the clinical trials that have examined new AD drugs, highlighting the development of new nanomedicines and the progress in their clinical translation. Nanotechnology‐based AD treatment is a nascent field, and a complete cure is distant at present; therefore, we also elaborate on the shortcomings of current AD nanomedicines. Finally, we discuss the prospects to guide the future development of AD nanomedicines.

Advancements and future directions in cardiac biomarker detection using lateral flow assays

“…Because chronic inflammation is a key factor for the development of atherosclerosis, increased CRP concentration can be a predictor of future vascular events. 97 However, the use of this biomarker in the clinical context is hindered by several limitations. 98 For example, elevated levels CRP can be associated to a number of inflammatory processes, making it difficult to ascertain the exact cause of its elevation.…”

“…Cheng et al 97 developed a sandwich immunoassay using quantum dots conjugated monoclonal anti-CRP antibodies. The reporters' fluorescence was measured using a portable fluorescence strip reader ESEQuant lateral flow system.…”

Deep Learning‐Enabled Multiplexed Point‐of‐Care Sensor using a Paper‐Based Fluorescence Vertical Flow Assay

“…Standard LFAs rely on a colorimetric detection modality where the optical contrast results from the absorption of the incident light by gold nanoparticle labels (AuNPs); [ 25 ] sensitivity limitations in such LFAs are imposed by the absorption properties of AuNPs and limited density of AuNP labels within the testing region of the sensor. [ 26 ] Various other optical modalities (e.g., fluorescence, [ 27–45 ] chemiluminescence, [ 26,46,47 ] surface‐enhanced Raman scattering, [ 48 ] signal amplification, [ 49–51 ] etc.) have also been employed in LFAs to replace AuNPs and achieve better sensitivity and quantitative analysis.…”

“…Compared to other modalities, fluorescence‐based LFA platforms are appealing high‐sensitivity assays that have relatively simple operation with a single sample injection step [ 27,28 ] and they have been successfully applied for quantifying biomarkers from biological samples; however, they often rely on expensive readout hardware [ 27–29,34,36,38,42,43,45 ] and have low throughput with one or two analytes per sensor. [ 27–38,42–45 ] The limitation in biomarker multiplexing mainly comes from the inline geometry of LFAs, which constrains the flow length of the loaded samples and can lead to depletion of reagents and nonuniformity when flowing past adjacent test lines in series. [ 31 ]…”

“…While some multiplexed paper‐based fluorescence assays have been reported in the literature, including assays for the quantification of cardiac markers, [ 26,28,34–36,38–45,47–51 ] they demonstrated sensing of at most two analytes [ 32,34,45 ] or employed relatively expensive benchtop readout hardware [ 30,31,36,39,40,42,43,45 ] (see Table S1, Supporting Information). Some of the highest sensitivity LFAs demonstrated for the detection of cardiac biomarkers of interest include fluorescence‐based tests with limits‐of‐detection (LODs) of, e.g., 0.01, 0.002, and 0.21 ng mL −1 for myoglobin, [ 40 ] CK‐MB, [ 40 ] and FABP, [ 44 ] respectively, however these assays employed relatively expensive readout for accurate quantitative analysis or could only detect a single analyte [ 44 ] (Table S1, Supporting Information).…”