Kui Wang

Cholinesterase-Responsive Supramolecular Vesicle

Enzyme-responsive, amphiphilic self-assembly represents one of the increasingly significant topics in biomaterials research and finds feasible applications to the controlled release of therapeutic agents at specific sites where the target enzyme is located. The supramolecular approach, using superamphiphiles, provides a smart way to fabricate drug delivery systems responsive to enzymatic catalysis. In this work based on the concept of supramolecular chemistry, we report an enzyme-responsive vesicle using p-sulfonatocalix[4]arene as the macrocyclic host and natural enzyme-cleavable myristoylcholine as the guest molecule. The complexation of p-sulfonatocalix[4]arene with myristoylcholine directs the formation of a supramolecular binary vesicle, which is dissipated by cholinesterase with high specificity and efficiency. Cholinesterase is a key protein overexpressed in Alzheimers disease, and therefore, the present system may have potential for the delivery of Alzheimers disease drugs.

Multistimuli Responsive Supramolecular Vesicles Based on the Recognition of p-Sulfonatocalixarene and its Controllable Release of Doxorubicin

We report the novel construction of nanosupramolecular binary vesicles based on host-guest complex formation between p-sulfonatocalix[4]arene and asymmetric viologen, which was identified by UV-vis and fluorescence spectroscopy, dynamic laser scattering, transmission electron microscopy, scanning electron microscopy, and surface tension experiments. The critical aggregation concentration of asymmetric viologen decreases pronouncedly by a factor of ca. 1000 owing to the complexation of p-sulfonatocalix[4]arene. Furthermore, we have demonstrated that the resulting vesicles can respond to multiple external stimuli, including temperature, host-guest inclusion, and redox. Methods of warming and inclusion of cyclodextrins were then employed to disrupt the vesicle architecture to release hydrophilic doxorubicin from the interior of the vesicle. Finally, cell experiments were performed to evaluate the cellular toxicity of the supramolecular binary vesicle and the anticancer efficiency of doxorubicin-loaded vesicle.

Highly effective binding of viologens by p-sulfonatocalixarenes for the treatment of viologen poisoning.

Viologens are showing an increasing number of scientific and technical applications in addition to their use as herbicides. However, their high toxicity poses considerable risks to human health, society, and the environment. In this context, we propose a new therapeutic protocol for the treatment of viologen poisoning. The mechanism of this new protocol is based on host-guest chemistry and involves the effective inhibition of viologen toxicity by the complexation of p-sulfonatocalix[n]arenes. NMR, ITC, and X-ray crystallography studies indicated that p-sulfonatocalix[n]arenes could form highly stable complexes with viologens. Electrochemical results showed that the highly effective binding could induce the reduction potentials of viologens to shift to more negative values. Further studies in mice showed that the ingestion of p-sulfonatocalix[n]arenes significantly decreased the mortality rate of viologen-poisoned mice with lung and liver protection. As a result, p-sulfonatocalix[n]arenes may have potential application in the clinical treatment of viologen poisoning.

Temperature-Controlled Supramolecular Vesicles Modulated by p-Sulfonatocalix[5]arene with Pyrene

Construction of vesicles is a significant topic of research in the fields of chemistry, biology, and materials science for their various applications. Recently, more and more research has been focused on “supramolecular amphiphiles”, which have emerged as a smart strategy due to their simplicity, versatility, and especially reversibility. Several kinds of noncovalent interactions have been used to tune the molecular amphiphilicity and self-assembled nanostructures, including hydrogen-bonding, charge-transfer, and p···p interactions, among others. The noncovalent interactions often employed (e.g., hydrogen bonding, coordination, and p stacking) are not always effective for designing supramolecular architectures in aqueous medium, and hence, they lack the necessary biocompatibility for applications in the fields of biotechnology. Macrocyclic receptors, such as cyclodextrins, calixarenes, and cucurbiturils, exhibit particular advantages in building water-soluble supramolecular architectures, more significantly, the three macrocyclic species are all friendly to organisms. To the best of our knowledge, supramolecular vesicles formed by host–guest interactions between macrocyclic hosts and guests have been explored less frequently. Kim et al. reported, for the first time, the spontaneous formation of vesicles triggered by the formation of a stable ternary inclusion complex that behaves as a large supramolecular amphiphile, in which cucurbituril was employed. Cyclodextrin is the macrocyclic host used most frequently in building organized amphiphiles, and the first noncovalent vesicle based on a cyclodextrin complex was reported by Chen and co-workers in 2007. Calixarenes, composed of phenolic units linked by methylene groups, represent a particularly significant class of the host molecules in supramolecular chemistry. Their intrinsic cone shape is the prerequisite for high-curvature aggregations of amphiphiles. Their relatively rigid framework can enhance the stability of amphiphilic aggregation. Consequently, calixarenes have received certain attention in constructing micellar and vesicular aggregations. The vesicles reported are uniformly formed by a covalent approach that modifies calixarenes into amphiphiles by the linkage of lipophilic groups at one rim and hydrophilic groups at the other rim, whereas no supramolecular vesicles based on host–guest complexation have been explored. Recently, Garc a-R o and Basilio found that the complexation of water-soluble calix[6]arene can tune the amphiphilicity of a cationic surfactant. Blanzat et al. reported the spontaneous formation of vesicles by combining an aminocalix[6]arene with sugar-based surfactants using an acid–base reaction to obtain a catanionic association while this manuscript was under preparation. Our particular interest herein is to fabricate calixarene-based supramolecular vesicles through host–guest complexation. The most fascinating aspect of supramolecular chemistry is that two or more components can self-assemble into higher-order structures, which exhibit particular properties and functions that the individual component cannot achieve. Herein, we report the successful construction of nanoscale supramolecular binary vesicles on the basis of host–guest complex formation between p-sulfonatocalix[5]arene (C5AS) and 1-pyrenemethylaminium (PMA) (Scheme 1). Notably, neither free C5AS nor PMA can form nanoscale aggregates themselves. Furthermore, the obtained vesicle shows thermal reversibility and it can disassemble when the temperature increases up to 35–40 8C. This temperature-responsive character makes this kind of vesicle a potential delivery model for special substrates. A simple mixture of C5AS (0.05 mm) and PMA (0.25 mm) with a charge-matching molar ratio in aqueous solution shows the Tyndall effect, which prompted us to explore the higher hierarchy aggregation based on the host–guest complexation of C5AS with PMA. The critical aggregation concentrations (CAC) of PMA in the absence and presence of C5AS were measured by monitoring the polarity of the sur[a] K. Wang, Dr. D.-S. Guo, Prof. Dr. Y. Liu Department of Chemistry State Key Laboratory of Elemento-Organic Chemistry Nankai University, Tianjin 300071 (P.R. China) Fax: (+86)22-23503625 E-mail : yuliu@nankai.edu.cn Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201000991.

A Supramolecular Vesicle Based on the Complexation of p-Sulfonatocalixarene with Protamine and its Trypsin-Triggered Controllable-Release Properties.

Enzyme-responsive assembly represents one of the increasingly significant topics in biomaterials research and finds feasible applications to the controlled release of therapeutic agents at specific sites at which the target enzymes are located. In this work, based on the concept of host-guest chemistry, a trypsin-responsive supramolecular vesicle using p-sulfonatocalix[4]arene as the macrocyclic host and natural serine protease trypsin-cleavable cationic protein protamine as the guest molecule, is reported. The complexation of p-sulfonatocalix[4]arene with protamine directs the formation of a supramolecular binary vesicle, which is dissipated by trypsin with high selectivity. Therefore, the present system represents a principle-of-concept to build a controlled-release carrier at trypsin-overexpressed sites.

Controlled Self‐Assembly by Mono‐p‐sulfonatocalix[n]arenes and Bis‐p‐sulfonatocalix[n]arenes

The complexation-induced critical aggregation concentrations of 1-pyrenemethylaminium by mono-p-sulfonatocalix[n]arenes and bis-p-sulfonatocalix[n]arenes (n=4, 5) were systemically measured by fluorescence spectroscopy. In all cases, the complexation-induced critical aggregation concentration decreases by about 3 times upon addition of p-sulfonatocalix[n]arenes. However, the optimal molar ratios for the aggregation of 1-pyrenemethylaminium by mono-p-sulfonatocalix[n]arenes and bis-p-sulfonatocalix[n]arenes are distinctly different: For mono-p-sulfonatocalix[n]arenes, the optimum mixing ratio for the aggregation of 1-pyrenemethylaminium is 1:4 mono-p-sulfonatocalix[n]arenes/1-pyrenemethylaminium, whereas only 2.5 molecules of 1-pyrenemethylaminium can be bound by one cavity of bis-p-sulfonatocalix[n]arenes. The intermolecular complexation of mono-p-sulfonatocalix[n]arenes and bis-p-sulfonatocalix[n]arenes with 1-pyrenemethylaminium led to the formation of two distinctly different nanoarchitectures, which were shown to be nanoscale vesicle and rod aggregates, respectively, by using dynamic laser scattering, TEM, and SEM. This behavior is also different from the fiber-like aggregates with lengths of several micrometers that were formed by 1-pyrenemethylaminium itself above its critical aggregation concentration. Furthermore, the obtained nanoaggregates exhibit benign water solubility, self-labeled fluorescence, and, more importantly, temperature responsiveness.