Calixarenes (CAs), representing the third generation of supramolecular hosts and one of the most widely studied macrocyclic scaffolds, offer (almost) unlimited structure and application possibilities due to their ease of modification, which allows one to establish a large molecular library as a material basis for diverse biomedical applications. Moreover, CAs and their derivatives engage in various noncovalent interactions for the facile recognition of guests including bioactive molecules and are also important building blocks for the fabrication of supramolecular architectures. In view of their molecular recognition and self‐assembly properties, CAs are extensively applied in biosensing, bioimaging, and drug/gene delivery. Additionally, some CA derivatives exhibit biological activities and can therefore be used as new therapeutic agents. Herein, we summarize the diverse biomedical applications of CAs including in vitro diagnosis (biosensing), in vivo diagnosis (bioimaging), and therapy.
Combining compliant electrode arrays in open-mesh constructs with hydrogels yields a class of soft actuator, capable of complex, programmable changes in shape. The results include materials strategies, integration approaches, and mechanical/thermal analysis of heater meshes embedded in thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) hydrogels with forms ranging from 2D sheets to 3D hemispherical shells.
The membrane transport mechanisms of cell-penetrating peptides (CPPs) are still controversial, and reliable assays to report on their internalization in model membranes are required. Herein, we introduce a label-free, fluorescencebased method to monitor membrane transport of peptides in real time. For this purpose, a macrocyclic host and a fluorescent dye forming a host−dye reporter pair are encapsulated inside phospholipid vesicles. Internalization of peptides, which can bind to the supramolecular host, leads to displacement of the dye from the host, resulting in a fluorescence change that signals the peptide uptake and, thus, provides unambiguous evidence for their transport through the membrane. The method was successfully validated with various established CPPs, including the elusive peptide TP2, in the presence of counterion activators of CPPs, and with a calixarene-based supramolecular membrane transport system. In addition, transport experiments with encapsulated host−dye reporter pairs are not limited to large unilamellar vesicles (LUVs) but can also be used with giant unilamellar vesicles (GUVs) and fluorescence microscopy imaging.
Phosphorylation and dephosphorylation of peptides by kinases and phosphatases is essential for signal transduction in biological systems, and many diseases involve abnormal activities of these enzymes. Herein, we introduce amphiphilic calixarenes as key components for supramolecular, phosphorylation-responsive membrane transport systems. Dye-efflux experiments with liposomes demonstrated that calixarenes are highly active counterion activators for established cell-penetrating peptides, with EC values in the low nanomolar range. We have now found that they can even activate membrane transport of short peptide substrates for kinases involved in signal transduction, whereas the respective phosphorylated products are much less efficiently transported. This allows regulation of membrane transport activity by protein kinase A (PKA) and protein kinase C (PKC), as well as monitoring of their activity in a label-free kinase assay.
Nitrogen
dioxide (NO2) detection is of great importance
because the emission of NO2 gas profoundly endangers the
natural environment and human health. However, a few challenges, including
lowering detection limit, improving response/recovery kinetics, and
reducing working temperature, should be further addressed before practical
applications. Herein, a series of N-doped graphene quantum dot (N-GQD)-modified
three-dimensional ordered macroporous (3DOM) In2O3 composites are constructed and their NO2 response properties
are studied. The results show that compared to pure 3DOM In2O3, reduced graphene oxide (rGO)/3DOM In2O3, and N-doped graphene sheets (NS)/3DOM In2O3, the N-GQDs/3DOM In2O3 sensing materials
exhibit higher NO2 responses with fast response and recovery
speed and low working temperature (100 °C). In addition, the
detection limit of NO2 response for the optimal N-GQDs/In2O3 sensor
is as low as 100 ppb. Upon exposure to CO, CH4, NH3, acetone, ethanol, toluene, and formaldehyde, only very weak
responses could be observed, indicating good selectivity for the synthesized
material. More attractively, the responses of the optimized N-GQDs/In2O3 sensor exhibit no obviously big fluctuation
over 60 days, implying good long-term stability. We suggest that the
formation of heterojunctions between 3DOM In2O3 and N-GQDs and the doping N atoms in N-GQDs play crucial roles in
improving the NO2 sensing properties.
We describe a platform for high-throughput
electrophoretic mobility
shift assays (EMSAs) for identification and characterization of molecular
binding reactions. A photopatterned free-standing polyacrylamide gel
array comprised of 8 mm-scale polyacrylamide gel strips acts as a
chassis for 96 concurrent EMSAs. The high-throughput EMSAs was employed
to assess binding of the Vc2 cyclic-di-GMP riboswitch to its ligand.
In optimizing the riboswitch EMSAs on the free-standing polyacrylamide
gel array, three design considerations were made: minimizing sample
injection dispersion, mitigating evaporation from the open free-standing
polyacrylamide gel structures during electrophoresis, and controlling
unit-to-unit variation across the large-format free-standing polyacrylamide
gel array. Optimized electrophoretic mobility shift conditions allowed
for 10% difference in mobility shift baseline resolution within 3
min. The powerful 96-plex EMSAs increased the throughput to ∼10
data/min, notably more efficient than either conventional slab EMSAs
(∼0.01 data/min) or even microchannel based microfluidic EMSAs
(∼0.3 data/min). The free-standing polyacrylamide gel EMSAs
yielded reliable quantification of molecular binding and associated
mobility shifts for a riboswitch–ligand interaction, thus demonstrating
a screening assay platform suitable for riboswitches and potentially
a wide range of RNA and other macromolecular targets.
Excess accumulation of amyloid-β (Aβ) protein in the brain is the primary pathogenesis of Alzheimer's disease (AD). Inhibition of Aβ fibrillation and disaggregation of Aβ fibrils is an attractive therapeutic and preventive strategy for Aβ-induced AD. Here, near infrared (NIR) light-responsive nanoparticles (NPs) composed of amphiphilic guanidinocalix[5]arene (GC5A), 4-(dodecyloxy)benzamido-terminated methoxy poly(ethylene glycol), and photothermal conjugated polymer PDPP are fabricated. The NIR lightresponsive NPs can efficiently penetrate the blood-brain barrier (BBB), inhibit amyloid-β 42 (Aβ42) fibrillation, and disaggregate fibrils after NIR light irradiation. Through the advantage of containing GC5A, the NPs exhibit extremely strong binding affinity for the Aβ42 protein. Interestingly, upon NIR light irradiation, benefiting from the high photothermal conversion efficiency of PDPP, NPs generate local heat and effectively promote the BBB permeability. Moreover, NPs are multifunctional platforms for the inhibition of Aβ42 fibrillation and disaggregation of fibrils after irradiation with NIR light, distinctly reducing cytotoxicity and eliminating Aβ42 plaques in the hippocampus of AD mice. Hence, NPs provide an interesting strategy for the inhibition and disaggregation of Aβ42 fibrillation and present an excellent therapeutic strategy for amyloidosis.
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