Metal–Organic Frameworks-Based Nanoplatform for Treatment of Breast Cancer

Nanoscaled metal–organic frameworks (MOFs) have great prospects in drug delivery. As a unique architecture, MOF-on-MOF has emerged as a promising strategy to enhance drug loading and release efficacy. Herein, a ZIF-8-on-ZIF-8 nanoplatform has been fabricated via the MOF-on-MOF strategy for doxorubicin (DOX) loading, resulting in a core–shell hierarchical nanostructure (DOX@ZIF-8-on-ZIF-8, DZZ). This unique nanoplatform exhibited pH and GSH dual-responsive DOX-releasing behavior, which are features of the tumor microenvironment (TME). Compared to monolayer DOX-encapsulated monolayer ZIF-8 (DOX@ZIF-8, DZ), DZZ can significantly increase the drug loading efficiency (DLE) by 56-fold, increase drug encapsulation efficiency (DEE) by 25-fold, enhance the penetration depth of DOX, and improve the selective inhibition on breast cancer 4T1 cells both in vitro and in vivo. Such a ZIF-on-ZIF nanoplatform provides an efficient strategy for tumor-targeted drug delivery and breast cancer treatments.