The incident happened around 10 p.m. in a residential Wyomissing neighborhood, near the Berkshire Mall.
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According to police, the man was taken to the hospital after the shooting. He died at the hospital just before 4 a.m. Tuesday, according to the Berks County coroner's office.
Police said the man's two young sons were home when two men tried breaking into his home on Birchwood Road. They were not injured.
According to investigators, the victim was able to call 911 and told responding officers the men pepper-sprayed him and attempted to enter the house.
The man was shot when he tried to push the intruders out, Wyomissing Police Chief Jeffery Biehl told WFMZ.
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Investigators were on scene through the night and are expected to remain at the home through the day Tuesday.
Police said they believe the house was targeted and it was an isolated incident.
Police are asking neighbors to contact them if they heard anything in the area around 10 p.m. or have security cameras.
Officials have not yet released the name of the victim.