Novel Biological Functions of ZIF‐NP as a Delivery Vehicle: High Pulmonary Accumulation, Favorable Biocompatibility, and Improved Therapeutic Outcome

Though zeolitic imidazole framework (ZIF) emerges as an advanced functional material for small‐molecule delivery due to its unique features such as high loading and pH‐sensitive degradation, there are extreme short of knowledge regarding its biological functions. To qualify this category of delivery vehicle, ZIF‐8 nanoparticles (ZIF‐NPs) with or without cargo are engineered and comprehensively investigated in vitro and in vivo. Interestingly, ZIF‐NPs demonstrate strong bioadhesion but with limited internalization themselves, which enhance the membrane‐mediated ROS and are different from that of inorganic ZnO inducing mitochondria‐mediated reactive oxygen species (ROS) without biomembrane damage. Unexpected high concentration is found in lung, probably due to the particle size and distribution of the nanocarriers; however, the drug levels drop dramatically with time, revealing the fast degradation and elimination. At the given doses, ZIF‐NPs exhibit reasonably biosafety in animal tests as evidenced by their acceptable system and blood biocompatibilities, and minimal impacts on the liver and renal functions, immune cells, inflammatory factors, etc. ZIF‐NPs with fluorouracil loading (5F@ZIF‐NPs) significantly improve the therapeutic outcome of lung metastasis tumor in a nude mice model. Generally, ZIF‐NPs demonstrate unique biological functions in terms of bio–nano interaction, pulmonary accumulation, biocompatibility, and antitumor therapy, which endow them potential as the delivery vehicles.