Loader.content.smoothing = true;

The line above triggers the so called pixel-level access to an image. Basically it's like using the BitmapData.draw() method. Images that don't reside in the same sandbox will through an exception when being loaded.

Is there a way to enable image smoothing on a static/global level?

This thing sucks big time. Image smoothing is nothing like data access... I can't understand why Adobe did this..