Statement of significance
Several human pro-apoptotic peptides (namely BAK, BAX and
PUMA) have been engineered as self-assembling protein
nanoparticles targeted to the tumoral marker CXCR4. The
systemic administration of the same final amounts of those
materials as single drugs, or as combinations of two or three of
them, shows disparate intensities of antitumoral effects in a
mouse model of human colorectal cancer, which are boosted in
the triple combination on a non-additive basis. The superiority
of the combined administration of pro-apoptotic agents, acting
at different levels of the apoptotic cascade, opens a plethora of
possibilities for the development of effective and selective
cancer therapies based on the precise cocktailing of pro-
apoptotic nanoparticulate agents.