A dual-pH sensitive drug release system for combinatorial delivery of 5‑fluorouracil and leucovorin calcium in colon cancer therapy

The synergistic effect of leucovorin calcium (LVCa) on 5-fluorouracil (5-FU) has been widely confirmed, but as far as we know, there is no effective way to simultaneously deliver LVCa and 5-FU to tumor sites. In this paper we innovatively established a dual-pH sensitive drug release system based on ZIF-8 frameworks decorated with hyaluronic acid-LVCa bioconjugates linked with an acid-cleavable hydrazone bond to achieve the combinatorial delivery and on-demand drug release of 5-fluorouracil (5-FU) and leucovorin calcium (LVCa) at the acidic pH conditions of the tumor sites. The as-obtained HA-LVCa/5-FU@ZIF-8 nanoplatforms load 0.35 g of 5-FU and 0.048 g of LVCa per gram and exhibited high inhibiting colon cells growth performance in vitro.