Chemotherapy is still an important and effective clinical treatment for cancer. However, individual drugs hardly achieve precise controlled release and targeted therapy, thus resulting in unavoidable side effects. Fortunately, the emergence of drug carriers is expected to solve the above problems. In this work, the MOF-on-MOF strategy was adopted to encapsulate DOX into double-layer NH 2 -MIL-88B to fabricate a core−shell-structured DOX@NH 2 -MIL-88B-On-NH 2 -MIL-88B (DMM) and then realize the pH and GSH dual-responsive controlled DOX release. Because of the core−shell structure, the drug-loading capacity of DMM reached 14.4 wt %, which was nearly twice that of DOX@ NH 2 -MIL-88B (DM), and the controlled release performance of DMM was also improved at the same time, greatly improving the kinetics equilibrium time of DOX from 2 h (DM) to 16 h (DMM) at pH 5.0. Moreover, we found that DMM also possessed peroxidase-like catalytic activity under acidic conditions, which could catalyze H 2 O 2 to produce • OH, exhibiting the potential chemodynamical treatment of cancer. Cell experiments showed that DMM had a significant inhibitory effect against 4T1 cancer cells, and the survival rate of 4T1 cells was less than 20% at 100 ppm.

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Controlling the crystal size and surface chemistry of MOF materials, and understanding their multifunctional effect are of great significance for the biomedical applications of MOF systems. Herein, we designed and synthesized a new anionic MOF, ZJU-64-NSN, which features 1D channels decorated with highly polarized thiadiazole groups, and its crystal size could be systematically tuned from 200 ​μm to 300 ​nm through a green and simple approach. As a result, the optimal nanosized ZJU-64-NSN is found to enable an ultrafast loading of cationic drug procainamide (PA) (21.2 ​wt% within 1 ​min). Moreover, the undesirable chemical stability of PA@ZJU-64-NSN is greatly improved by the surface coating of polyethylene glycol (PEG) biopolymer. The final drug delivery system PEG/PA@ZJU-64-NSN is found to effectively prevent PA from premature release under the harsh stomach environments due to the intense host-guest interaction, and mainly release PA to the targeted intestinal surroundings. Such controlled drug delivery is proved to be triggered by endogenic Na + ions instead of H + ions, well revealed by the study on the dynamics behavior of drug release and UV–Vis absorption spectrum. Good biocompatibility of ZJU-64-NSN and PEG-coated ZJU-64-NSN has been fully demonstrated by MTT assay as well as confocal microscopy imaging.

Combination therapy has shown great potential for effective cancer treatment. In this work, anticancer drug curcumin (Cur) and photothermal agent indocyanine green (ICG) have been encapsulated into the pH-responsive ZIF-8 simultaneously to obtain ICG&Cur@ZIF-8 through one-pot synthesis method. The drug loading capacity was estimated as 9.6 and 12.3 wt% for Cur and ICG, respectively. As expected, ICG&Cur@ZIF-8 exhib-ited the pH-responsive ICG and Cur delivery, which was ascribed to the decomposition of ZIF-8 in acidic environment. Moreover, ICG&Cur@ZIF-8 also showed the high photothermal performance due to the efficient encapsulation of ICG. The codelivery of two therapeutic agents may bring more opportunities for biomedical application.