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.