A Pd2L4 Metallacage‐Cored Supramolecular Amphiphile and Its Application in Dual‐Responsive Controllable Release

Comprehensive Summary The construction of multi‐responsive supramolecular systems for drug delivery is a challenging task. In this work, a Pd2L4 metallacage 1·([BF4]−)4 with four pyrene units was first designed and synthesized through coordination‐driven self‐assembly. After the introduction of γ‐CD, a supramolecular amphiphile 1–γ‐CD was successfully constructed based on the host–guest molecular recognition between γ‐CD and the pyrene unit of 1·([BF4]−)4, which further self‐assembled into dual‐responsive supramolecular vesicles in aqueous solution. DOX·HCl was used as a model molecule to study the drug encapsulation and release behavior of the supramolecular vesicles. By adjusting the pH of the solution to acidic condition or adding a certain amount of α‐amylase, the vesicle structure was destroyed to achieve rapid and effective release of the drug molecules. This study provides an example for the rational design of efficient dual‐responsive supramolecular nanocarriers, which have potential application value in the field of controlled drug delivery. In this work, dual‐responsive supramolecular vesicles were constructed by palladium(II) coordination‐driven self‐assembly and γ‐CD‐based host–guest molecular recognition, which were applied to the encapsulation and controlled release of anticancer drug DOX·HCl.