Improvement of Cell Penetrating Peptide for Efficient siRNA Targeting of Tumor Xenografts in Zebrafish Embryos

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Laroui, Nabila | Cubedo, Nicolas | Cao, Anne-Marinette | Rossel, Mireille | Bettache, Nadir

Edité par CCSD ; Wiley -

Une correction à cet article a été publiée sous le DOI 10.1002/adtp.202100139, contenant les informations suivantes : The authors regret that the author Anne-Marinette Cao was originally missing in the authorship. They also apology for an error in the footnote of table 2 and in the Supporting Information Figure S2. The updated Supporting Information is now available from the Wiley Online Library. The correct and complete information now appear here:Nabila Laroui, Nicolas Cubedo, Anne-Marinette Cao, Mireille Rossel, Nadir Bettache*N. Laroui, A.-M. Cao,# Dr. N. BettacheInstitut des Biomolécules Max Mousseron, UMR 5247, University of Montpellier, CNRS, ENSCM, 15, avenue Charles Flahault, BP14491, F-34093 Montpellier cedex 5, FranceE-mail: nadir.bettache@umontpellier.fr# Current address: École Polytechnique Fédérale de Lausanne (EPFL), SB ISIC LCBM, Station 6, 1015 Lausanne, SwitzerlandAcknowledgement : A-M. Cao is a recipient of the EpiGenMed Labex doctoral fellowship, University of MontpellierTable 2: CPP/siRNA nanoparticles were formed at R = 20 using a siRNA concentration of 40 nM in water for mean size acquisition.". International audience. Cell-penetrating peptides (CPPs) are one of the most efficient vectors for achieving cellular uptake of different cargos. However, their application in cancer therapy is greatly limited due to the lack of tissue selectivity, as they are widely distributed in most tissues following in vivo administration. To introduce specificity and improve tumor targeting, a combination of a cell-penetrating peptide (CADY) and a targeting ligand, the laminin receptor binding peptide (YIGSR) to target the 37/67 kDa laminin receptor, known to be upregulated in most cancer cells and to be correlated with the invasiveness and metastatic potential, is formulated. The targeting CPP named “Y-CADY” does not induce any change in the physico-chemical properties (secondary structure, small interference RNA (siRNA) complexation, size, and charge) of CADY. Interestingly, Y-CADY is more efficient than CADY for gene silencing in cell lines, and more potent for targeting and for inducing apoptosis of tumor xenografts in zebrafish embryos. The present study demonstrates that the novel targeting CPP “Y-CADY” is efficient for gene silencing and can serve as a vector to target cancer cells in vivo.

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