Chenhao Yao

Dramatically Promoted Swelling of a Hydrogel by Pillar[6]arene–Ferrocene Complexation with Multistimuli Responsiveness

The swelling-shrinking transition of hydrogels is crucial for their wide applications such as actuators and drug delivery. We hereby fabricated a smart hydrogel with ferrocene groups on pendant of polymer networks. While it was immersed in the water-soluble pillar[6]arene (WP6) aqueous solution, the hydrogel was dramatically swollen, which was an approximately 11-fold promotion in weight compared with that in pure water, due to the formation of the inclusion complexes between WP6 and ferrocene groups in the hydrogel. In particular, the well-swollen hydrogel exhibited good responsiveness to multistimuli including temperature, pH, redox, and competitive guests by tuning the dissociation/formation of WP6-ferrocene inclusion complexes or the strength of their charges. Meanwhile, potential application of such a smart hydrogel in pH-responsive drug release was demonstrated as well.

Dual-Responsive Bola-Type Supra-Amphiphile Constructed from Water-Soluble Pillar[5]arene and Naphthalimide-Containing Amphiphile for Intracellular Drug Delivery

Supramolecular construction of multistimuli platform for drug delivery is a challenging task. In this work, a pH and GSH (glutathione) dual-responsive bola-type supramolecular amphiphile was successfully fabricated by the complexation between a water-soluble pillar[5]arene (WP5) and a bolaform naphthalimide guest (G) in water. The resulting bola-type amphiphile further self-assembled into supramolecular binary vesicles, which could be disassembled by low pH, a high-GSH-concentration environment, or both. Furthermore, the results of drug loading and releasing tests showed that doxorubicin (DOX), the hydrophobic anticancer drug, could be successfully encapsulated into the Stern region of the obtained supramolecular vesicles and generated the DOX-loaded vesicles with good drug-loading efficiency. Moreover, the obtained DOX-loaded vesicles displayed efficient and rapid DOX release at a simulated tumor microenvironment with low-pH or excess-GSH conditions or both. Significantly, cytotoxicity experiments revealed that the DOX-loaded supramolecular vesicles could obviously improve the anticancer efficiency of free DOX for tumor cells while remarkably reducing its side effects for normal cells. In vitro cellular uptake and subcellular localization assays further proved that these smart drug nanovehicles, entering cancer cells mainly via endocytosis, could cause excellent drug accumulation in cancer cells. The present study provides a successful example with which to rational design an effective bola-type stimuli-responsive supramolecular nanocarrier, which might have wide potential applications in the construction of various controlled drug-delivery systems.

Thermo- and oxidation-responsive supramolecular vesicles constructed from self-assembled pillar[6]arene-ferrocene based amphiphilic supramolecular diblock copolymers

Novel thermo- and oxidation-responsive supramolecular polymeric vesicles in water were constructed from amphiphilic supramolecular diblock copolymers at 37 °C via pillar[6]arene-ferrocene based host–guest interaction, in which the host polymer was pillar[6]arene-terminal-modified poly(N-isopropylacrylamide) (PNIPAM-P[6]) synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization and the guest polymer was ferrocene-terminal-modified methoxy-poly(ethylene glycol) (mPEG-Fc). The host polymer formed micelles in water at 25 °C, and upon addition of guest mPEG-Fc, a hydrophilic supramolecular diblock copolymer PNIPAM-P[6] ⊃ mPEG-Fc was formed, which could become amphiphilic when heated to 37 °C and further self-assembled into supramolecular polymeric vesicles. The resulting vesicles exhibited good thermo- and oxidation-responsiveness, due to the solubility of the host polymer at different temperatures and the oxidation of the ferrocene moiety of the guest polymer, respectively. More importantly, the supramolecular polymeric vesicles could be further applied in the encapsulation of an anticancer drug (doxorubicin hydrochloride) and its controlled release in response to temperature and oxidizing agents.

Glucose‐Responsive Supramolecular Vesicles Based on Water‐Soluble Pillar[5]arene and Pyridylboronic Acid Derivatives for Controlled Insulin Delivery

The stimuli-responsive behavior of supramolecular nanocarriers is crucial for their potential applications as smart drug delivery systems. We hereby constructed a glucose-responsive supramolecular drug delivery system based on the host-guest interaction between a water-soluble pillar[5]arene (WP5) and a pyridylboronic acid derivative (G) for insulin delivery and controlled release under physiological conditions. The approach represents the ideal treatment of diabetes mellitus. The drug loading and in vitro drug release experiments demonstrated that large molecular weight insulin could be encapsulated into the vesicles with high loading efficiency, which, to our knowledge, is the first example of small-size supramolecular vesicles with excellent encapsulation capacity of a large protein molecule. Moreover, FITC-labeled insulin was used to evaluate the release behavior of insulin, and it was demonstrated that high glucose concentration could facilitate the quick release of insulin, suggesting a smart drug delivery system for potential application in controlled insulin release only under hyperglycemic conditions. Finally, we demonstrated that these supramolecular nanocarriers have good cytocompatibility, which is essential for their further biomedical applications. The present study provides a novel strategy for the construction of glucose-responsive smart supramolecular drug delivery systems, which has potential applications for the treatment of diabetes mellitus.

A Four-Armed Unsymmetrical Cryptand: From Two Different Host–Guest Interactions to Responsive Supramolecular Polymer

By linking BMP32C10 and DB24C8 motifs together, a four-armed cryptand 1 is synthesized successfully, in which BMP32C10 motif can bind paraquat 2 while DB24C8 motif can complex dibenzylammonium salt 3 in spite of the electrostatic repulsion between guests 2 and 3. The base/acid-responsive supramolecular polymer is constructed further via two kinds of host-guest interactions between cryptand 1 and two homoditopic paraquat 4 and dibenzylammonium salt 5 similar to guests 2 and 3.