G4-Quartet hydrogel loaded with doxorubicin and hemin for cascade chemodynamic therapy

Abstract

The efficiency of CDT for cancer treatment is significantly reduced due to the low concentration of H₂O₂ inside the cancer cell and the poor water solubility of the traditional CDT agents. Hence, it is extremely important to develop a facile strategy for the crafting of stimuli-responsive and biocompatible nanostructures that permit the efficient co-delivery of CDT and H₂O₂ generating agents. Herein, we report a single-step supramolecular approach for the synthesis of a stimuli-responsive nanoformulation of G₄ hydrogel loaded with Hem and Dox (G₄/Hem/Dox hydrogel) for CDT applications. Enhanced peroxidase-like activity is observed for the G₄/Hem/Dox hydrogel. Efficient internalization of the nanoformulation into cancerous cells and excellent therapeutic efficiency is demonstrated. The remarkable therapeutic efficacy for the nanoformulation is attributed to the combined effects of (i) excellent CDT activity of G₄/Hem/Dox hydrogel, (ii) the chemotherapeutic effect of Dox and (iii) the cascade CDT of free Dox and Hem. This work highlights the potential of nucleobase-derived nanostructures as a biocompatible and stimuli-responsive nanoscaffold for the delivery of multiple therapeutic agents for drug delivery.