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Growth of ZIF-8 Nanoparticles In Situ on Graphene Oxide Nanosheets: A Multifunctional Nanoplatform for Combined Ion-Interference and Photothermal Therapy.

The regulation of intracellular ions' overload to interrupt normal bioprocesses and cause cell death has been developed as an efficient strategy (named as ion-interference therapy/IIT) to treat cancer. In this study, we design a multifunctional nanoplatform (called BSArGO@ZIF-8 NSs) by in situ growth of metal organic framework nanoparticles (ZIF-8 NPs) onto the graphene oxide (GO) surface, subsequently reduced by ascorbic acid and modified by bovine serum albumin. This nanocomplex causes the intracellular overload of Zn2+, an increase of reactive oxygen species (ROS), and exerts a broad-spectrum lethality to different kinds of cancer cells. BSArGO@ZIF-8 NSs can promote cell apoptosis by initiating bim (a pro-apoptotic protein)-mediated mitochondrial apoptotic events, up-regulating PUMA/NOXA expression, and down-regulating the level of Bid/p53AIP1. Meanwhile, Zn2+ excess triggers cellular dysfunction and mitochondria damage by activating the autophagy signaling pathways and disturbing the intracellular environmental homeostasis. Combined with the photothermal effect of reduced GO (rGO), BSArGO@ZIF-8 NSs mediated ion-interference and photothermal combined therapy leads to effective apoptosis and inhibits cell proliferation and angiogenesis, bringing a higher efficacy in tumor suppression in vivo. This designed Zn-based multifunctional nanoplatform will allow promoting further the development of IIT and the corresponding combined cancer therapy strategy.