Integrated supramolecular nanovalves for photothermal augmented chemodynamic therapy through strengthened amplification of oxidative stress

The amplified oxidative stress strategy has been emerged as one promising method to enhance the chemodynamic therapy (CDT) efficacy due to the H2O2 up-regulation and glutathione (GSH) down-regulation behavior in tumor cells. However, how to further achieve the satisfied CDT efficacy is still a big challenge. In this paper, the supramolecular nanovalves (SNs) with oxidative amplification agents cinnamaldehyde-(phenylboronic acid pinacol ester) conjugates (CA-BE) encapsulated inside were developed to accelerate and amplify the generation of ·OH and consumption of GSH while augmenting the CDT efficacy. SNs were obtained through ferrocene/Au modified mesoporous silica nanoparticles (MSN@Au-Fc) and active targeting β-cyclodextrin modified hyaluromic acid (HA-CD). After CD44 receptor-mediated cellular internalization, the CA-BE were released to elevate H2O2 amount and consume GSH for the desired generation of higher cytotoxic hydroxyl radicals (·OH). Moreover, the NIR-activated MSN@Au-Fc can increase the temperature for the accelerated and amplified oxidative stress. As such, the therapeutic efficacy of our synthesized CA-BE and the accompanied hyperthermia were augmented toward synergistically inhibiting tumor growth.