Pore Space Partition Approach of ZIF-8 for pH Responsive Codelivery of Ursolic Acid and 5-Fluorouracil

Metal–organic frameworks are smart carriers for controlled drug delivery due to large surface area and adjustable pore size. Current approaches can hardly utilize the pore space of MOFs thoroughly, greatly causing the waste of pore space. Here, the Pore Space Partition (PSP) approach was employed to achieve the effective encapsulation and pH-controlled codelivery of two guest molecules. The pore space of ZIF-8 was partitioned by encapsulation of the large molecule ursolic acid (UA), and the remaining pore space was filled with the small molecule 5-fluorouracil (5-FU), obtaining 5-FU&UA@ZIF-8 with high loading capacity of UA (12.80 wt %) and 5-FU (11.20 wt %). Accompanied by the collapse of ZIF-8 in acidic surroundings, 5-FU&UA@ZIF-8 exhibited the pH-controlled UA delivery. To our surprise, 5-FU&UA@ZIF-8 also showed the pH responsive 5-FU delivery, which did not exist before pore space partition by UA. Codelivery of 5-FU and UA enable 5-FU&UA@ZIF-8 to have good anticancer performance against 4T1 cells.