Extracellular vesicles (EVs) have
emerged as important carriers
for intercellular communication and biological sources for diagnosis
and therapeutics. Low efficiency in EV isolation from biofluids, however,
severely restricts their downstream characterization and analysis.
Here, we introduced a novel strategy for EV isolation from urine for
prostate cancer diagnosis using bifunctionalized magnetic beads through
high affinity Ti(IV) ions and the insertion of a phospholipid derivative,
1,2-distearoyl-sn-glycero-3-phosphoethanolamine,
into the EV membrane synergistically. We demonstrated its efficient
isolation of EVs from urine samples with low contamination, high recovery
(>80%), and short separation time (within 1 h), resulting in the
identification
of 36,262 unique EV peptides corresponding to 3302 unique proteins
and 3233 unique phosphopeptides representing 1098 unique phosphoproteins
using only 100 μL and 5 mL urine samples, respectively. Coupled
with trapped ion mobility spectrometry and parallel accumulation–serial
fragmentation for phosphosite-specific resolution, quantitative phosphoproteomics
of urine samples from prostate cancer patients and healthy individuals
revealed 121 upregulated phosphoproteins in cancer patients in contrast
to the healthy group. These particular advantages indicate that the
novel bifunctional material enables sensitive EV phosphoproteomic
analysis for noninvasive biomarker screening and early cancer diagnosis.
Alzheimer's disease is still incurable and neurodegenerative, and there is a lack of detection methods with high sensitivity and specificity. In this study, by taking different month old Alzheimer's mice as models, we have explored the possibility of the target bioimaging of diseased sites through the initial injection of zinc gluconate solution into Alzheimer's model mice post-tail vein and then the combination of another injection of ferrous chloride (FeCl) solution into the same Alzheimer's model mice post-stomach. Our observations indicate that both zinc gluconate solution and FeCl solution could cross the blood-brain barrier (BBB) to biosynthesize the fluorescent zinc oxide nanoclusters and magnetic iron oxide nanoclusters, respectively, in the lesion areas of the AD model mice, thus enabling high spatiotemporal dual-modality bioimaging (i.e., including fluorescence bioimaging (FL) and magnetic resonance imaging (MRI)) of Alzheimer's disease for the first time. The result presents a novel promising strategy for the rapid and early diagnosis of Alzheimer's disease.
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