We report a ligand decoration strategy to enlarge the lattice dilation of quantum dots (QDs), which greatly enhances the characteristic sensitivity of a QD-based thermometer. Upon a multiple covalent linkage of macrocyclic compounds with QDs, for example, thiolated cyclodextrin (CD) and CdTe, the conformation-related torsional force of CD is conducted to the inner lattice of CdTe under altered temperature. The combination of the lattice expansion/contraction of CdTe and the stress from CD conformation change greatly enhances the shifts of both UV-vis absorption and photoluminescence (PL) spectra, thus improving the temperature sensitivity. As an example, β-CD-decorated CdTe QDs exhibit the 0.28 nm shift of the spectra per degree centigrade (0.28 nm/°C), 2.4-fold higher than those of monothiol-ligand-decorated QDs.
The effect of the length of ROCK (Rho-associated kinase) on its oligomerization state has been investigated by analysing full-length protein and four truncated constructs using light-scattering and analytical ultracentrifugation methods. Changes in size correlate with the kinetic properties of the kinase. Sedimentation velocity, sedimentation equilibrium and light-scattering data analyses revealed that protein constructs of size Ser6-Arg415 and larger exist predominantly as dimers, while smaller constructs are predominantly monomeric. The amino acid segments comprising residues 379-415 and 47-78 are shown to be necessary to maintain the dimeric ROCK structure. kcat values ranged from 0.7 to 2.1 s(-1) and from 1.0 to 5.9 s(-1) using ROCK peptide (KKRNRTLSV) and the 20000 Da subunit of myosin light chain respectively as substrate, indicating that the effect of the ROCK oligomerization state on the kcat is minor. Values of ATP K(m) for monomeric constructs were increased by 50-80-fold relative to the dimeric constructs, and K(i) comparisons using the specific competitive ROCK inhibitor Y-27632 also showed increases of at least 120-fold, demonstrating significant perturbations in the ATP binding site. The corresponding K(m) values for the ROCK peptide and myosin light chain substrates increased in the range 1.4-16-fold, demonstrating that substrate binding is less sensitive to the ROCK oligomerization state. These results show that the oligomerization state of ROCK may influence both its kinase activity and its interactions with inhibitors, and suggest that the dimeric structure is essential for normal in vivo function.
Cytosolic protein delivery is a prerequisite for protein‐based biotechnologies and therapeutics on intracellular targets. Polymers that can complex with proteins to form nano‐assemblies represent one of the most important categories of materials, because of the ease of nano‐fabrication, high protein loading efficiency, no need for purification, and maintenance of protein bioactivity. Stable protein encapsulation and efficient intracellular liberation are two critical yet opposite processes toward cytosolic delivery, and polymers that can resolve these two conflicting challenges are still lacking. Herein, hyperbranched poly(β‐amino ester) (HPAE) with backbone‐embedded phenylboronic acid (PBA) is developed to synchronize these two processes, wherein PBA enhanced protein encapsulation via nitrogen–boronate (N–B) coordination while triggered polymer degradation and protein release upon oxidation by H2O2 in cancer cells. Upon optimization of the branching degree, charge density, and PBA distribution, the best‐performing A2‐B3‐C2‐S2‐P2 is identified, which mediates robust delivery of various native proteins/peptides with distinct molecular weights (1.6–430 kDa) and isoelectric points (4.1–10.3) into cancer cells, including enzymes, toxins, antibodies, and CRISPR‐Cas9 ribonucleoproteins (RNPs). Moreover, A2‐B3‐C2‐S2‐P2 mediates effective cytosolic delivery of saporin both in vitro and in vivo to provoke remarkable anti‐tumor efficacy. Such a potent and universal platform holds transformative potentials for protein pharmaceuticals.
It is highly desired to develop new antibacterial agents with superior bactericidal efficiency for minimizing the damage to biological cells. We developed a combined antibacterial nanohybrid exhibiting a superb bactericidal effect and excellent biocompatibility by integrating upconversion nanoparticles (UCNPs) with silver nanoclusters (AgNCs). UCNPs and methylene blue (MB) molecules were encapsulated with silica microspheres via microemulsion, with MB as the photosensitizer. Silver ions (Ag + ) were reduced by amino groups on the surface of silica spheres, wherein silver nanoclusters (AgNCs) were formed in situ to produce the nanohybrid, UCNPs@SiO 2 (MB)@AgNCs. UCNPs emit visible light at 655 nm under excitation by near-infrared radiation (NIR, 980 nm). MB absorbs the emission from UCNPs to generate toxic singlet oxygen ( 1 O 2 ), which leads to the apoptosis of bacteria cells. Meanwhile, silver ions released from AgNCs destroy the bacteria membrane structure. Upon NIR irradiation at 980 nm for 10 min, 8.33 μg mL −1 nanohybrid results in a 100% killing rate for both Gram-positive S. aureus (+) and Gram-negative E. coli (−).
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