3 research outputs found
Quantification of Cancer Biomarkers in Serum Using Scattering-Based Quantitative Single Particle Intensity Measurement with a Dark-Field Microscope
In this work, we
developed a simple yet robust single particle
scattering intensity measurement method for the quantification of
cancer-related biomarkers. The design is based on the plasmonic coupling
effect between noble metal nanoparticles. First, the primary and secondary
antibodies were conjugated onto the surface of 60 nm gold nanoparticles
(AuNPs, act as capture probes) and 50 nm silver nanoparticles (AgNPs,
act as signal amplification probes) respectively. In the presence
of corresponding antigen, a sandwiched immunocomplex was formed, resulting
a significantly enhanced scattering intensity in contrast to that
of individual probes. By measuring the intensity change of the particles
with a dark-field microscope (DFM), the amount of target protein could
be accurately quantified. As a proof of concept experiment, quantification
of three types of antigens, including carcinoembryonic antigen (CEA),
prostate-specific antigen (PSA) and alpha fetoprotein (AFP) by this
platform was demonstrated with limit of detection (LOD) of 1.7, 3.3,
and 5.9 pM, respectively, with a linear dynamic range of 0 to 300
pM. Furthermore, to elucidate the potential in clinical application,
the content of antigens in a serum sample was also quantified directly
without additional sample pretreatment. In order to validate the reliability
of this method, the measured result was also compared with that obtained
by regular enzyme-linked immunosorbent assay (ELISA) kit, showing
good consistency between these two data sets. Therefore, owing to
the simplicity and accuracy of this method, it could be potentially
applied for massive disease screening in clinical assay in the future
A Zero Cross-Talk Ratiometric Two-Photon Probe for Imaging of Acid pH in Living Cells and Tissues and Early Detection of Tumor in Mouse Model
Acid–base
disorders disrupt proper cellular functions, which
are associated with diverse diseases. Development of highly sensitive
pH probes being capable of detecting and monitoring the minor changes
of pH environment in living systems is of considerable interest to
diagnose disease as well as investigate biochemical processes in vivo.
We report herein two novel high-resolution ratiometric two-photon
(TP) fluorescent probes, namely, PSIOH and PSIBOH derived from carbazole–oxazolidine
Ï€-conjugated system for effective sensing and monitoring acid
pH in a biological system. Remarkably, PSIOH exhibited the largest
emission shift of ∼169 nm from 435 to 604 nm upon pH changing
from basic to acidic with an ideal p<i>K</i><sub>a</sub> value of 6.6 within a linear pH variation range of 6.2–7.0,
which is highly desirable for high-resolution tracking and imaging
the minor fluctuation of pH in live cells and tissues. PSIOH also
exhibits high pH sensitivity, excellent photostability, and reversibility
as well as low cytotoxicity. More importantly, this probe was successfully
applied to (i) sense and visualize the pH alteration in HeLa cells
caused by various types of exogenous stimulation and (ii) detect and
differentiate cancer and tumors in liver tissues and a mouse model,
realizing its practical <i>in vitro</i> and <i>in vivo</i> applications
Effective Theranostic Cyanine for Imaging of Amyloid Species in Vivo and Cognitive Improvements in Mouse Model
We report herein an
investigation of carbazole-based cyanine,
(<i>E</i>)-4-(2-(9-(2-(2-methoxyethoxy)Âethyl)-9<i>H</i>-carbazol-3-yl)-vinyl)-1-methyl-quinolin-1-iumiodide (SLM), as an
effective theranostic agent for Alzheimer’s disease (AD). This
cyanine exhibited desirable multifunctional and biological properties,
including amyloid-β (Aβ)-oligomerization inhibition, blood–brain
barrier permeability, low neurotoxicity, neuroprotective effect against
Aβ-induced toxicities, high selectivity and strong binding interactions
with Aβ peptide/species, good biostability, as well as strong
fluorescence enhancement upon binding to Aβ species for diagnosis
and therapy of AD. This cyanine has been successfully applied to perform
near-infrared in vivo imaging of Aβ species in transgenic AD
mouse model. The triple transgenic AD mice intraperitoneally treated
with SLM showed significant recovery of cognitive deficits. Furthermore,
those SLM-treated mice exhibited a substantial decrease in both of
oligomeric Aβ contents and tau proteins in their brain, which
was attributed to the induction of autophagic flux. These findings
demonstrated for the first time that SLM is an effective theranostic
agent with in vivo efficacy for diagnosis and treatment of AD in mouse
models