Glucose-Responsive ZIF-8 Nanocomposites for Targeted Cancer Therapy through Combining Starvation with Stimulus-Responsive Nitric Oxide Synergistic Treatment

With the rapid development of nanomedicine, low side effects and high-efficiency green antitumor approaches have attracted great attention. Herein, we report a strategy for the in situ synthesis of graphene oxide@zeolitic imidazolate framework-8 (GOx@ZIF-8) composite nanoparticles with high catalytic efficiency, under mild conditions by adding GOx molecules to the precursor of ZIF-8, and use them as a carrier to achieve efficient loading of l-Arg. In addition. folic-acid-conjugated bovine serum albumin (FA-BSA) has been used to engineer the surface of GOx@ZIF-8-l-Arg composite nanoparticles to enhance their specific recognition of tumor cells. With the high glucose level and low pH in the tumor intracellular environment, FA-BSA/GOx@ZIF-8-l-Arg rapidly consumed the intracellular glucose and produced H₂O₂, which profusely deteriorated the intracellular environment. Subsequently, a large amount of l-Arg was continuously released from the nanoparticles, reacting with H₂O₂ to continuously produce a high concentration of nitric oxide (NO), which further damaged the tumor cells. The FA-BSA/GOx@ZIF-8-l-Arg composite nanoparticles were cleverly designed to kill cancer cells efficiently through a starvation-NO synergistic process. This emerging green antitumor method has a promising application prospect in targeted therapy for the efficient clearance of cancers.