Extreme
rarity and inherent heterogeneity of circulating tumor
cells (CTCs) result in a tremendous challenge for the CTC isolation
from patient blood samples with high efficiency and purity. Current
CTC isolation approaches mainly rely on the epithelial cell adhesion
molecule (EpCAM), which may significantly reduce the ability to capture
CTCs when the expression of EpCAM is lost or down-regulated in epithelial–mesenchymal
transition. Here, a rapid and highly efficient method is developed
to isolate and identify heterogeneous CTCs with high efficiency from
patient blood samples using the fluorescent-magnetic nanoparticles
(F-MNPs). A dual-antibody interface targeting EpCAM and N-cadherin
is fabricated onto the F-MNPs to capture epithelial CTCs as well as
mesenchymal CTCs from whole blood samples. The poly(carboxybetaine
methacrylate) brushes of excellent antifouling properties are employed
to decrease nonspecific cell adhesion. Moreover, the F-MNPs provide
a prompt identification strategy for heterogeneous CTCs (F-MNPs+,
Hoechst 33342+, and CD45−) that can directly identify CTCs
in a gentle one-step processing within 1 h after isolation from patient
blood samples. This has been demonstrated through artificial samples
as well as patient samples in details.
Near-infrared
(NIR) fluorescent probes can deeply penetrate through tissues with
little damage. To facilitate image-guided theranostics, researchers
usually apply a desired amount of photosensitizers to achieve effective
photothermal responses. However, these probes could easily suffer
from low photostability and aggregated-caused quenching effect in
high concentrations. In this paper, the rational incorporation of
an aggregated-induced emission (AIE) unit into the structure of heptamethine
cyanine IR-780 is reported. Using tetraphenylethene (TPE) as an AIE
core, we synthesize three TPE-modified IR-780 probes (IR-780 AIEgens)
via different linkages. The IR-780 derivatives all show enhanced AIE
features, in which the probe with an ether linkage (IR780-O-TPE) is
superior in rapid cell uptake, high targeting capacity, and good photostability.
Moreover, IR780-O-TPE exhibits the strongest cytotoxicity to HeLa
cells (IC50 = 3.3 μM). The three IR-780 derivatives
displayed a photothermal response in a concentration-dependent manner,
in which IR-780 AIEgens are more cytotoxic than IR-780, with IC50 of 0.3 μM under 808 nm laser irradiation. In tumor-bearing
mice, the optimal probe IR780-O-TPE also showed a more effective photothermal
response than IR-780. By illustrating the relationship between aggregation
state with photophysical properties, cell imaging, and cytotoxicity,
this work is helpful in modulating NIR-based photosensitizers into
AIE features for efficient image-guided theranostics.
Extensive
attention has been recently focused on designing signal
adjustable biosensors. However, there are limited approaches available
in this field. In this work, to visually track lysosomes with high
contrast, we used the i-motif structure as a pH-responsive unit and
proposed a novel strategy to regulate the fluorescence resonance energy
transfer (FRET) response of the pH sensor. By simply splitting the
i-motif into two parts and modulating the split parameters, we can
tune the pH transition midpoint (pHt) from 5.71 to 6.81
and the signal-to-noise ratio (S/N) from 1.94 to 18.11. To facilitate
the lysosome tracking, we combined the i-motif split design with tetrahedral
DNA (Td). The obtained pH nanosensor (pH-Td) displays appropriate
pHt (6.12) to trace lysosomes with high S/N (10.3). Benefited
from the improved stability, the superior cell uptake and lysosomal
location of pH-Td, the visualization of the distribution of lysosomes,
the lysosome–mitochondria interaction, and the pH changes of
lysosomes in response to different stimuli were successfully achieved
in NIH 3T3 cells. We believe that the design concept of controlling
the split sequence distance will provide a novel insight into the
design of i-motif-based nanosensors and even inspire the construction
of smart DNA nanodevices for sensing, disease diagnosis, and controllable
drug delivery.
Reliable
and accurate glucose detection in biological samples is
of great importance in clinical diagnosis and medical research. Chemical
probes are advantageous in simple operation and flexible design, especially
for the development of fluorescent probes. Anthracene-based diboronic
acid (P-DBA) has shown potential in glucose probing because of its
high sensitivity. However, poor solubility limits its applications
in aqueous media. In this work, we systemically modify P-DBA by introducing
fluoro (F-), chloro (Cl-), methoxyl (MeO-), or cyano (CN-) substituents.
Among these probes, the cyano-substituted probe (CN-DBA) displays
the highest glucose-binding constant (6489.5 M–1, 33% MeOH). More importantly, it shows good water solubility in
the aqueous solution (0.5% MeOH), with ultrasensitive recognition
with glucose (LOD = 1.51 μM) and robust sensing from pH 6.0
to 9.0. Based on these features, the CN-DBA is finally applied to
detect glucose in cell lysates and plasma, with satisfactory recovery
and precision. These results demonstrate that CN-DBA could serve as
an accurate, sensitive fluorescent probe for glucose assays in biological
samples.
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