TFEB Nucleus Translocation And Pro-survival Autophagy Induced By Zeolitic Imidazolate Framework-8

A great variety of nanoparticles are known to induce autophagy,leading to either pro-death or pro-survival consequences.Zeolitic imidazolate framework-8?ZIF-8?,a porous nanoparticle and a promising drug carrier,reportedly induced autophagy while delivering drugs,but whether the ZIF-8 nanoparticles per se could elicit an autophagic response was unclear.Here we show that ZIF-8 induced genuine autophagy in He La cells,characterized by increased autophagosome formation without disruption of autophagic flux,in a time-and dose-dependent fashion.Autophagy induced by ZIF-8 facilitated cell survival,as blockage of autophagy by either 3-MA or Atg 5 knockout significantly enhanced ZIF-8-facilitated He La cell death.ZIF-8 also elicited dephosphorylation and nucleus translocation of the transcription factor EB?TFEB?,an event that promoted lysosome biogenesis and was necessary for autophagy induction.We further pinpointed the inhibition of m TORC1 and elevation of intracellular Ca⁺⁺concentration as the mechanism underlying ZIF-8-elicited TFEB nucleus translocation.Our results revealed the unique ability of ZIF-8 in inducing pro-survival autophagy in cancer cells,a finding with important implications for potential clinical studies that utilize ZIF-8 as the drug carrier.