Supple 1. Characterization of both FeNPs

(A) TEM image, (B) XRD image

Supple 2. General images following exposure of both FeNPs

TEM images were made at 24 h after exposure.

Supple 3. Changes which are observed in FACS analysis

Cells was incubated for 24 h without or with both types of FeNPs (50 μg/ml), and total cells was harvested.FSCaxis indicate the cell size, and SSC axis indicate the increase of the granules.

Supple 4. Penetration of NM-FeNPs into ER within the cells

ER was localized by staining calnexin (green) which was embedded in the ER membrane.800× magnification. We can show indicate NM-FeNPs (red arrow) in the ER (white arrow).

Supple 5. A summary of genes regulated by more 2 fold in each cells

Cells were incubated for 1 h or 24 h without or with two types ofFeNPs(50 μg/ml). Total RNA which is extracted from 9 dishes was pooled to make one sample for test, respectively.(A) A summary, (B) The correlation between genes changed by both types of FeNPs at 1 h after exposure, (C) The correlation between genes changed by both types of FeNPs at 24 h after exposure

Supple 6.List of 30 genes which is the most up-regulated at 24 h after exposure

Cells were incubated for 1 h without or with two types ofFeNPs(50 μg/ml). Total RNA which is extracted from 9 dishes was pooled to make one sample for test, respectively.Analysis was performed one time,respectively.

Supple 7.List of 30 genes which is the most down-regulated at 24 h after exposure

Supple 8.Changes of protein expression following exposure of both types of FeNPs

The experiment was performed three times, independently, and all results showed similar trends. Representative data was presented, respectively.

Supporting information

Western blotting

Cell pellet was homogenized with a protein extraction solution (iNtRON Biotech,Kyunggi-do, Korea) and the lysate was acquired from centrifugation at 13,000 rpm for 30 min. The protein concentration was measured by the bicinchonic acid method (Sigma-Aldrich) and equal amounts of protein were separated on a 1% sodium dodecyl sulfate/ polyacrylamide gel and then transferred to a nitrocellulose membrane (HybondECL; Amersham Pharmacia Biotech, NJ, USA). Blots were blocked for 1 h at RT with 5% (w/v) non-fat dried milk in TBST. The membranes were immunoblotted with specific primary antibodies (1:1000 dilution): rabbit polyclonal antibody for microtubule-associated protein 1 light chain 3 (LC3) and poly (ADP-ribose) polymerase (PARP, Cell Signaling Technology), and beclin 1 (Santa Cruz Biotech), and goat polyclonal antibody for β-actin (Santa Cruz Biotech). The blots were then incubated with the corresponding conjugated anti-rabbit or anti-goat immunoglobulin G-horseradish peroxidase (1:2000 dilution, Invitrogen).Immunoreactive proteins were detected with the ECL Western Blotting Detection System.