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Borghese's collection includes works as diverse as Early Renaissance altarpieces such as Fra Angelico's Last Judgment (ca 1450); examples of northern art such as two paintings of Venus (early 16th century) by Lucas Cranach; sixteenth-century Venetian paintings such as Titian's Sacred and Profane Love (1514); and classicizing pictures such as Domenichino's Diana (1616/7).
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Even though later generations dispersed some of his acquisitions through sales and diplomatic gifts, the works that he assembled form the core of the holdings of the Galleria Borghese (Rome), a museum housed in the villa commissioned by Scipione (1613–15) from the architect Giovanni Vasanzio.
He is best known for participating in (and winning) the Peking to Paris race in 1907, accompanied by the journalist Luigi Barzini, Sr. and Ettore Guizardi, the prince's chauffeur, who apparently did most of the driving.