Delivery of Peptide Nucleic Acids Using an Argininocalix[4]arene as Vector

Cationic Calix[4]arene Vectors to Efficiently Deliver AntimiRNA Peptide Nucleic Acids (PNAs) and miRNA Mimics

“…First of all, the calix[4]arene vectors display reproducible differences in their transfection activity, when both U251 and HT29 cell lines are considered. For instance, in the case of PNA delivery, Arg-Hex , Gu-Oct , Lys-Hex and GuPent-Hex exhibit the highest transfection efficiencies, similar to those displayed by PNAs functionalized with the octaarginine (R8) peptide [ 29 , 84 ]. Interestingly, Gu-Hex displays a lower transfection efficiency when compared with Gu-Oct .…”

“…We have already reported that Arg-Hex , the lead compound from this class of vectors, exhibited low toxicity and no inhibitory effects on the growth of treated cells, unlike the gold-standard lipofectamine, which caused the inhibition of cell growth, as expected from the results of several reports. More importantly, a PNA against microRNA miR-221-3p fully maintained its biological activity and specificity in inhibiting the target miR-221-3p-mediated effects (i.e., induction of apoptosis) [ 83 , 84 ]. These important issues have been recently discussed in Finotti et al [ 84 ].…”

“…More importantly, a PNA against microRNA miR-221-3p fully maintained its biological activity and specificity in inhibiting the target miR-221-3p-mediated effects (i.e., induction of apoptosis) [ 83 , 84 ]. These important issues have been recently discussed in Finotti et al [ 84 ]. The preservation of the biological activity has been fully confirmed in the case of calix[4]arene-delivered pre-miRNA molecules [ 82 ].…”

miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review

“…(3) 2 0 -fluoro PNA the pseudo-peptide backbone is composed of unnatural N-(2aminoethyl)glycine units resistance to both nucleases and proteases; hybridize with high affinity to complementary sequences of singlestranded RNA and DNA, forming Watson-Crick double helices Gambari 55 Finotti et al 56 Nielsen et al 57 Demidov et al 58 Patel 59 LNA links the 2 0 -oxygen and 4 0 -carbon of ribose reducing the conformational flexibility of nucleotides increases their binding affinity Obika et al 60 Oieni et al 61 Di Martino et al 62 Gallo Cantafio et al By the use of their animal model, the authors demonstrated an antitumor activity induced by miR-221 targeting with AMO. 52 An advanced further method has been used to deliver peptide nucleic acids (PNA) targeting miR-221-3p based on a macrocyclic multivalent tetra argininocalix [4]arene used as a non-covalent vector for anti-miR-221-3p PNAs.…”

“…52 An advanced further method has been used to deliver peptide nucleic acids (PNA) targeting miR-221-3p based on a macrocyclic multivalent tetra argininocalix [4]arene used as a non-covalent vector for anti-miR-221-3p PNAs. The high delivery efficiency, low cytotoxicity, maintenance of the PNA biological activity, and easy preparation make this vector a candidate for a universal delivery system for this class of nucleic acid analogs, as has been recently reviewed by Finotti et al 56 Even though with innovative chemical modification, the progression into the clinic of ASOs has been questioned by different authors for their susceptibility to nucleases and fast clearance, the experts in the field have been induced to search for delivery systems to specifically target tissues. These attempts included nano-carriers with different chemistry (i.e., neutral lipids, PEGylation) or conjugation to different moieties, non-viral nano-carriers, and, to overcome immunogenicity, biomimetic nanovesicles (NVs).…”