Tumor-targeting semi-rigid metal-organic-polymer framework nanoparticles with high adaptability and bioavailability

In nature, most bio-tissues combine specific structural stability with functional adaptability. This unique virtue can help drug carriers endure various complicated microenvironments and biomembranes. So, we integrated flexible thermo-responsive polymer chains with upper critical solution temperature (UCST) into a rigid porous metal-organic framework to construct bioinspired copper-based dual-responsive metal-organic-polymer framework (MOPF) nanoparticles for targeted anti-tumor treatment. This MOPF nanocarrier exhibited significant drug-loading (9.03%) and encapsulation efficiency (96.40%), as well as high adaptivity and bioavailability. Under the dual stimulation of hyperthermia (43 °C) and high glutathione (GSH) concentration (10 mM) similar to a tumor microenvironment, its cumulative drug release rapidly reached 65.82% in 24 hours, along with simultaneous structural dissociation. By a catalyzed Fenton-like reaction, the copper ions exposed from MOPF were further induced to generate a large number of hydroxyl radicals and then exhaust GSH with high cell apoptosis (cell survival: 4.70%). Such semi-rigid MOPF microstructures not only realized the merging of chemotherapy, chemodynamic therapy, and copper toxicity therapy but also provided an innovative strategy to adapt a therapeutic process for a multifunctional drug carrier.