Hollow Mesoporous Silica@Metal–Organic Framework and Applications for pH‐Responsive Drug Delivery

: Metal--organic frameworks (MOFs), a new type of porous crystalline material, hold great potential in biomedical applications, such as drug delivery. However, the efficacy of drug delivery is limited by low drug loading. In this work, we synthesized hollow mesoporous silica (HMS)@MOF capsules that can be used as a pH-responsive drug delivery system for the anticancer drug doxorubicin (DOX). DOX is loaded into the inner cavity of HMS. Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles are then coated on the outer surface of the DOX-loaded HMS. The obtained material is a capsule (denoted as DOX/HMS@ZIF), in which DOX is encapsulated. The DOX/HMS@ZIF can be used as an efficient pH-responsive drug delivery system. DOX is not released under physiological conditions (pH 7.4), but is released at low pH (4-6) from DOX/HMS@ZIF. The DOX/HMS@ZIF capsule shows much higher cytotoxicity than free DOX and alters the delivery pathway for DOX in cancer cells, while the drug-free HMS@ZIF shows excellent biocompatibility. This opens new opportunities to construct a safe and efficient delivery system for targeted molecules using pH-responsive release for a wide range of applications.