A Dual pH-Gated Nanoplatform Enabled by Schiff Base Chemistry on ZIF-90 for a Synergistic Anticancer Effect In Vitro

Combination chemotherapy is a key strategy for improving cancer treatment efficacy and overcoming drug resistance, but it requires smart nanocarriers capable of codelivering multiple drugs and achieving precise release at the tumor site. Herein, we report a ZIF-90-based dual-drug delivery platform (NAR@ZIF-90-DOX) for synergistic cancer therapy. The natural product naringenin (NAR) was encapsulated within ZIF-90 pores via a “one-pot” method, while the chemotherapeutic drug doxorubicin (DOX) was covalently grafted onto the surface through a pH-sensitive Schiff base linkage. This dual-gated design leverages the acidic tumor microenvironment to trigger simultaneous ZIF-90 degradation and Schiff base cleavage. This enables the synchronous and targeted release of both drugs in 4T1 cells, leading to a significantly enhanced synergistic anticancer effect compared to single-drug administration. This work provides a strategy for designing multifunctional, intelligent Metal–Organic Frameworks (MOFs) nanoplatforms for combination chemotherapy.