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.
In Good Intentions, when Zachariah and his angels attack Bobby Singer's colony, the defenders kill many of the angels with weapons loaded with angel-killing bullets. Bobby arms Mary Winchester with a gun loaded with the bullets as well, but she is disarmed by Zachariah before she can use the gun on him.