Supramolecular Self-Assemblies with Self-Supplying H₂O₂ and Self-Consuming GSH Property for Amplified Chemodynamic...

Fe-based chemodynamic therapy (CDT) has become one potential method for cancer therapy due to its lower side effect and tumor-specific property. During the process of CDT, the lack of active targeting and biodegradable ability, insufficient endogenous H₂O₂, and overexpressed GSH in the tumor were responsible for the unsatisfactory therapeutic performance. Hence, we report host-guest interaction-based supramolecular polymers (HGSPs) that were constructed with the biomacromolecule β-cyclodextrin-grafted hyaluronic acid (HA-CD) as the active targeting host unit and hydrophobic ROS-responsive ferrocene-(phenylboronic acid pinacol ester) (Fc-BE) as the guest unit. HGSPs can further self-assemble into self-assemblies (HGSAs) and encapsulate PA as the prooxidant. After CD44-receptor-mediated cellular internalization, HGSAs could disassemble and release PA to elevate the H₂O₂ level for the production of higher cytotoxic hydroxyl radicals (^•OH) through the Fc-induced Fenton reaction. Moreover, quinone methide (QM) was generated to downregulate antioxidant GSH. The enhancement of H₂O₂ and consumption of GSH were favorable for CDT due to the amplified oxidative stress. In vivo experimental results indicated that HGSAs@PA might be used as an active targeting amplified CDT agent.