Tumor-targeting Semi-rigid Metal-organic-polymer Framework Nanoparticles with High Adaptability and Bioavailability

Abstract

In nature, most bio-tissues combine specific structural stability with functional adaptability. This unique virtue can help drug carrier to endure various complicated microenvironments and biomembranes. So we integrated flexible thermo-responsive polymer chains with upper critical solution temperature (UCST) into rigid porous metal-organic framework, to construct a bioinspired copper-based dual-responsive metal-organic-polymer framework (MOPF) nanoparticle for targeted anti-tumor treatment. This MOPF nanocarrier exhibited significant drug-loading (9.03%) and encapsulation efficiency (96.4%), as well as high adaptivity and bioavailability. Under the dual stimulation of hyperthermia (43 ˚C) and high glutathione (GSH) concentration (10 mM) alike to tumor microenvironment, its cumulative drug release rapidly reached 65.82% in 24 hours, along with the simultaneous structural dissociation. By catalyzed Fenton-like reaction, those copper ions exposed from MOPF further induced to generate a large number of hydroxyl radicals, and then to 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 innovational strategy to adapt therapeutic process for multifunctional drug carrier.