Robust Hydrogen-Bonded Organic Framework for pH-Responsive Drug Delivery

Hydrogen-bonded organic frameworks (HOFs), by virtue of their low toxicity, wide substrate tolerance, porosity, and regenerative and biocompatible traits, are an emerging class of porous polymeric materials that show great potential for intracellular delivery of chemotherapeutics. However, stability issues coupled with controlled release of a drug under desired stimuli have restricted their therapeutic potential. In the present study, based on density functional theory calculations predicting strong noncovalent interactions between the H-bonded 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tribenzoic acid (H₃TATB) dimer and the chemotherapeutic drug doxorubicin (Dox), we prepared a robust and reticular nanoplatform Dox@nano-HOF 1, which released Dox at low pH, making it an ideal carrier for targeted drug delivery to tumor sites sparing the normal tissues. Additionally, the cytotoxic and apoptosis assays confirmed the efficacy of the nanocarrier in inducing dose-dependent cell death in cancer cells. This study opens up new and hitherto unexplored avenues for the use of robust HOFs in pH-responsive delivery of anticancer therapeutics.