Reactive Oxygen Species and Glutathione Dual Redox-Responsive Supramolecular Assemblies with Controllable Release Capability

A dual redox and biorelevant triggered supramolecular system is developed through noncovalent supramolecular inclusion interactions between the ferrocene (Fc) modified on camptothecin (CPT) and beta-cyclodextrin (beta-CD) at the end of methoxy polyethylene glycol (mPEG). With these two segments, a stable noncovalent supramolecular structure, i.e., mPEG-beta-CD/Fc-CPT, can be formed, and then self-assembled into micellar structures in water. Interestingly, these supramolecular micelles showed uniform sphere structure, high and constant drug loading content, hyper-fast redox-responsive drug release, and exhibited equal cellular proliferation inhibition toward A549 cancer cells. The cytotoxicity evaluation of mPEG-beta-CD also indicated good biocompatibility. In vivo results revealed the mPEG-beta-CD/Fc-CPT nanoparticles had higher in vivo efficacy without side effects. It is anticipated this supramolecular complex may serve as a new kind of promising alternative for drug delivery systems.