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.