GSH/pH dual-responsive supramolecular hybrid vesicles for synergistic enzymatic/chemo-tumor therapy

Abstract Supramolecular amphiphilic vesicles are promising carriers in tumor therapy due to their excellent loading capabilities for both hydrophilic and hydrophobic cargos, especially for biomacromolecules such as proteins, enzymes and plasmids. However, the poor circulating stability and unsatisfied therapeutic efficiency greatly limit their in vivo applications. To address these issues, herein, we design and develop a new kind of GSH/pH dual-responsive supramolecular hybrid vesicles (SHVs) to encapsulate and deliver simultaneously biomacromolecule glucose oxidase (GOD) and chemotherapeutic drug docetaxel (DTX) for synergistic enzymatic/chemo-tumor therapy. The SHVs are constructed by the self-assembly of β-CD-poly(e-caprolactone), ferrocene-poly (acrylic acid) and pillar [5] arenes via the terminal β-CD/Fc host-guest interaction, followed by cross-linking with 3-mercaptopropyltrimethoxysilane and poly (ethylene glycol) modification. As a vehicle for both hydrophilic and hydrophobic cargos, the resulting GOD/DTX co-loaded SHVs exhibit excellent synergistic enzymatic/chemo-tumor therapeutic ability with a combination index (CI = 0.285) of GOD and DTX in cellular level and high tumor inhibitory rate of 95.3% in vivo. Consequently, the resulting hybrid vesicles can be used as efficient and safe carriers for biomacromolecules in further cancer therapy.