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In the Middle Ages it was converted into a major fortification, although most of the original Roman structure was preserved. Pope Nicholas III connected the castle to St. Peter's Basilica by a covered corridor called Passetto di Borgo.
The castle was involved in numerous sieges, including that of Pope Clement VII by the forces of the Holy Roman Empire, in 1527, in which Benvenuto Cellini was a participant.
Sant'Angelo also served as a prison. One of its prisoners was Giordano Bruno, who had been imprisoned here for 6 years.
Now the castle is a museum.