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 tu-mor 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 incorpo-rating 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 ac-etal 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. (c) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

This study successfully fabricated supramolecular complexes self-assemblies (SCSAs) by incorporating cinnamaldehyde (CA) and PEG-modified cyclodextrin host units (mPEG-CD-CA) with ferrocene-(phenylboronic acid pinacol ester) conjugates (Fc-BE) based on CD-induced host-guest interactions. After internalization by cancer cells, CA can be released from SCSAs through pH-responsive acetal linkage, elevating the H2O2 level by activating NADPH oxidase. Furthermore, Fc can catalyze the H2O2 to higher cytotoxic hydroxyl radicals (OH), while quinone methide (QM) can be produced and consume the antioxidant GSH. In vitro and in vivo experiments demonstrate that SCSAs can be potential amplified CDT nanoagents.