The following seems to work for your first question:
Grid[{{a, Grid[{{1, 2, 3}, {4, 5, 6}, {7, 8, 9}}], b}, {c, d, e}},
ItemSize -> {3, 3}, Frame -> All, Spacings -> {1, 1},
ItemStyle -> {"FontFamily" -> "Helvetica",
Automatic, {{1, 1} -> Directive[Red, 20, Bold], {1, 3} ->
Directive[Green, 20, Bold], {2, 2} ->
Directive[Blue, 20, Bold]}}]
I wonder why this other way the matrix gets mangled:
Grid[{{a, Grid[{{1, 2, 3}, {4, 5, 6}, {7, 8, 9}}], b}, {c, d, e}},
ItemSize -> {3, 3}, Frame -> All, Spacings -> {1, 1},
ItemStyle -> {Automatic,
Automatic, {{1, 1} -> Directive[Red, 20, Bold], {1, 3} ->
Directive[Green, 20, Bold], {2, 2} ->
Directive[Blue, 20, Bold]}},
BaseStyle -> "FontFamily" -> "Helvetica"]