RESUMEN
The refractoriness of tumor cells to apoptosis represents the main mechanism of resistance to chemotherapy. Smac/DIABLO mimetics proved to be effective in overcoming cancer-acquired resistance to apoptosis as a consequence of overexpression of the anti-apoptotic proteins XIAP, cIAP1, and cIAP2. In this work, we describe a dual-targeting peptide capable of selectively activating apoptosis in cancer cells. The complex consists of a fluorescent periodic mesoporous organosilica nanoparticle that carries the short sequences of Smac/DIABLO bound to the αvß3-integrin ligand. The dual-targeting peptide @PMO shows significantly higher toxicity in αvß3-positive HeLa cells with respect to αvß3-negative Ht29 cells. @PMO exhibited synergistic effects in combination with oxaliplatin in a panel of αvß3-positive cancer cells, while its toxicity is overcome by XIAP overexpression or integrin ß3 silencing. The successful uptake of the molecule by αvß3-positive cells makes @PMO promising for the re-sensitization to apoptosis of many cancer types.