In "The Great Escapist", Crowley reveals his new invention, an Angel-Killing Gun which he produced by melting down angel blades. He demonstrated its effectiveness by killing Esper and wounding Ion. He also shot Castiel with a bullet in order to retrieve the Angel Tablet hidden inside his stomach.
Castiel used that same bullet he was shot with to kill Ion by forcing it into Ion's eye.
When Dean tried to use the gun on Lucifer, the bullets prove ineffective.
- Although not yet shown, the bullets are likely effective against everything that can be killed by an angel blade, like Hellhounds.