Host-guest interactions based supramolecular complexes self-assemblies for amplified chemodynamic therapy with H₂O₂ elevation and GSH consumption properties

Although endogenous H₂O₂ is overexpressed in tumor tissue, the amount of endogenous H₂O₂ is still insufficient for chemodynamic therapy (CDT). In addition, the abundant cellular glutathione (GSH) could also consume ^•OH for reduced CDT. Thus, the elevation of H₂O₂ and the consumption of GSH in tumor tissue are essential for the increased ^•OH yield and amplified CDT efficacy. In this paper, host-guest interactions based supramolecular complexes self-assemblies (SCSAs) were fabricated by incorporating cinnamaldehyde (CA) and PEG-modified cyclodextrin host units (mPEG-CD-CA) with ferrocene-(phenylboronic acid pinacol ester) conjugates (Fc-BE) on the basis of CD-induced host-guest interactions. After being internalized by cancer cells, CA can be released from SCSAs through the pH-responsive acetal linkage, elevating the H₂O₂ level by activating NADPH oxidase. Then, Fc can catalyze the H₂O₂ to higher cytotoxic hydroxyl radicals (^•OH). Moreover, quinone methide (QM) can be produced through H₂O₂-induced aryl boronic ester rearrangement and further consume the antioxidant GSH. In vitro and in vivo experiments demonstrate that SCSAs can be provided as potential amplified CDT nanoagents.