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

Frontiers in Pharmacology

Pharmacology

Sigrid Simonetti¹  Rossella De Marco¹  Weizhe Huang¹  Annalisa Ferino²  Eros Di Giorgio²  Luigi Xodo² 

[1] Department of Agricultural, Food, Environmental and Animal Sciences (Di4A), University of Udine, Udine, Italy;Department of Medicine, University of Udine, Udine, Italy;

关键词: Smac mimetics;    nanoparticles;    caspases;    oxaliplatin;    cervical cancer;    colorectal cancer;    integrin αvβ3;   

DOI  :  10.3389/fphar.2023.1237478

 received in 2023-06-09, accepted in 2023-08-07,  发布年份 2023

来源: Frontiers

【 摘 要 】

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 αvβ3–integrin ligand. The dual-targeting peptide @PMO shows significantly higher toxicity in αvβ3-positive HeLa cells with respect to αvβ3-negative Ht29 cells. @PMO exhibited synergistic effects in combination with oxaliplatin in a panel of αvβ3-positive cancer cells, while its toxicity is overcome by XIAP overexpression or integrin β3 silencing. The successful uptake of the molecule by αvβ3-positive cells makes @PMO promising for the re-sensitization to apoptosis of many cancer types.

【 授权许可】

Unknown   
Copyright © 2023 Di Giorgio, Ferino, Huang, Simonetti, Xodo and De Marco.