AUTHOR=Di Giorgio Eros , Ferino Annalisa , Huang Weizhe , Simonetti Sigrid , Xodo Luigi , De Marco Rossella 

TITLE=Dual-targeting peptides@PMO, a mimetic to the pro-apoptotic protein Smac/DIABLO for selective activation of apoptosis in cancer cells

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1237478

DOI=10.3389/fphar.2023.1237478

ISSN=1663-9812

ABSTRACT=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 over-expression of the anti-apoptotic proteins XIAP, cIAP1, 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 organosilicate nanoparticles that carries the short sequences of SMAC/Diablo bond with the v3-integrin ligand SMAC/Diablo bound the v3-integrin ligand. The dual-targeting peptide@PMO shows significant higher toxicity in v3 positive HeLa cells in respect to with respect tov3 negative Ht29 cells. @PMO exhibited synergistic effects in combination with Oxaliplatin in a panel of v3 positive cancer cells, while its toxicity is overcome by XIAP over-expression or integrin 3 silencing. The successful uptake of the molecule by v3 positive cells makes @PMO promising for the re-sensitization to apoptosis of many cancer types.