pH/ROS Dual-Responsive Supramolecular Vesicles Fabricated by Carboxylated Pillar[6]arene-Based Host–Guest Recognition and Phenylboronic Acid Pinacol Ester Derivative

The pH and reactive oxygen species (ROS) dual-responsive supramolecular vesicle utilizing a novel host-guest molecular recognition between a phenylboronic acid pinacol ester derivative carrying long alkyl chain (PBEC12A) and carboxylated pillar[6]arene (CP[6]) is developed. The host-guest complexation between CP[6] and PBEC12A was first studied in aqueous solution. PBEC12A was encapsulated within CP[6] forming a stable host-guest complex with a binding constant as high as 106 M-1 order of magnitude. The driving force behind such a host-guest recognition was the combination of electrostatic interaction and hydrophobic effect. Then, the self-assembly of the supra-amphiphiles of PBEC12A-CP[6] host-guest complexes was investigated in aqueous solution through high-resolution transmission electron microscope and dynamic light scattering. It was found that the supra-amphiphiles self-assembled into supramolecular vesicles and the size of the self-assembled supramolecular vesicles could be tuned from 25 to 200 nm by varying the ratio of CP[6] to PBEC12A. To demonstrate the pH- and ROS-responsive properties of the self-assembled vesicles, the supramolecular vesicles self-assembled from PBEC12A/CP[6] (5:1) were utilized. The Nile Red loading and release studies demonstrated that the supramolecular vesicles possessed good pH/ROS dual-responsive properties. This study enriches the field of supra-amphiphile based on noncovalent interactions. It is anticipated that the pH/ROS dual-responsive supramolecular vesicles have potential applications in drug-delivery systems because both the stimuli are in close relation with specific microenvironments of tumors and relevant diseases of the human body.