Expanding the Hydrophobic Cavity Surface of Azocalix[4]arene to Enable Biotin/Avidin Affinity with Controlled Release.

The development of artificial receptors that combine ultrahigh-affinity binding and controllable release for active guests holds significant importance in biomedical applications. On one hand, a complex with an exceedingly high binding affinity can resist unwanted dissociation induced by dilution effect and complex interferents within physiological environments. On the other hand, stimulus-responsive release of the guest is essential for precisely activating its function. In this context, we expanded hydrophobic cavity surface of a hypoxia-responsive azocalix[4]arene, affording Naph-SAC4A. This modification significantly enhanced its aqueous binding affinity to 1013 M-1, akin to the naturally occurring strongest recognition pair, biotin/(strept-)avidin. Consequently, Naph-SAC4A emerges as the first artificial receptor to simultaneously integrate ultrahigh recognition affinity and actively controllable release. The markedly enhanced affinity not only improved Naph-SAC4A's sensitivity in detecting rocuronium bromide in serum, but also refined the precision of hypoxia-responsive doxorubicin delivery at the cellular level, demonstrating its immense potential for diverse practical applications.

Alleviating Recombinant Tissue Plasminogen Activator-induced Hemorrhagic Transformation in Ischemic Stroke via Targeted Delivery of a Ferroptosis Inhibitor.

Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) is the primary treatment for ischemic stroke. However, rtPA treatment can substantially increase blood-brain barrier (BBB) permeability and susceptibility to hemorrhagic transformation. Herein, the mechanism underlying the side effects of rtPA treatment is investigated and demonstrated that ferroptosis plays an important role. The ferroptosis inhibitor, liproxstatin-1 (Lip) is proposed to alleviate the side effects. A well-designed macrocyclic carrier, glucose-modified azocalix[4]arene (GluAC4A), is prepared to deliver Lip to the ischemic site. GluAC4A bound tightly to Lip and markedly improved its solubility. Glucose, modified at the upper rim of GluAC4A, imparts BBB targeting to the drug delivery system owing to the presence of glucose transporter 1 on the BBB surface. The responsiveness of GluAC4A to hypoxia due to the presence of azo groups enabled the targeted release of Lip at the ischemic site. GluAC4A successfully improved drug accumulation in the brain, and Lip@GluAC4A significantly reduced ferroptosis, BBB leakage, and neurological deficits induced by rtPA in vivo. These findings deepen the understanding of the side effects of rtPA treatment and provide a novel strategy for their effective mitigation, which is of great significance for the treatment and prognosis of patients with ischemic stroke.

A novel fluorescent nano-chemosensor for cesium ions based on naphthalene macrocyclic derivative.

A new macrocyclic nano-chemosensor (L) was synthesized and characterized by common spectroscopic methods. Spectral properties of fluorescent macrocycle L were studied either as solution in ethanol or as insoluble nanoparticles in aqueous buffer solution. The nano-chemosensors with size about 40nm were prepared by nanoprecipitation method. The influence of metal cations such as Na(+), K(+), Cs(+), Mg(2+), Ba(2+), Al(3+), Pb(2+), Cr(3+), Mn(2+), Fe(3+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+) and Ag(+) on the spectroscopic properties of the chemosensor in aqueous buffer solution were investigated by means of emission spectrophotometry. The macrocycle was found to be as an effective fluorescence sensor for Cs(+) ions.

A novel fluorescent nano-chemosensor for Al(III) ions using a new macrocyclic receptor.

A novel macrocyclic chemosensor (L) has been synthesized and characterized by common spectroscopic methods. Spectral properties of fluorescent macrocycle L were studied either as solution in ethanol or as insoluble nanoparticles in aqueous buffer solution. The nano-chemosensors with size about 35nm were prepared by nanoprecipitation method. The influence of metal cations such as Na(+), K(+), Cs(+), Mg(2+), Ba(2+), Al(3+), Pb(2+), Cr(3+), Mn(2+), Fe(3+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+) and Ag(+) on the spectroscopic properties of nano-chemosensor (L) in aqueous buffer solution were investigated by means of emission spectrophotometry. The macrocycle was found to be as an effective fluorescence sensor for Al(3+) ions.