Arginine-tagging of Polymeric Nanoparticles Via Histidine to Improve Cellular Uptake
Chiu, Jasper; Tucker, Ian; McDowell, Arlene; McLeod, Bernie
Polyarginine, a cell-penetrating peptide, has been shown to aid cellular penetration of bioactives into cells. We utilized a novel approach of using a histidine linker to produce poly(ethyl-cyanoacrylate) (PECA) nanoparticles tagged with oligoarginine and investigated cellular uptake. MALDI TOF/TOF (tandem) analysis revealed that di-arginine-histidine (RRH) covalently bound to PECA nanoparticles to form cationic particles (+18 mV), while longer oligoarginine peptides did not co-polymerize with PECA nanoparticles. Although RRH-tagged nanoparticles had similar size and FITC-dextran entrapment efficiency compared to unmodified nanoparticles, RRH-tagging of nanoparticles resulted in a greater release of FITC-dextran. As the nanoparticles were found to aggregate in Hanks Balanced Salt Solution (HBSS), the effect of phosphate on the zeta-potential of nanoparticles was studied. Treating the nanoparticles with poloxamer-407 prevented aggregation. RRH-tagged PECA nanoparticles increased cellular uptake by a further 30% compared to unmodified PECA nanoparticles and was concentration dependent. We suggest that enhanced cell uptake can be achieved using a di-arginine histidine construct as opposed to the previously published findings that a minimum of hexa-arginine is necessary. Further, the cationic zeta-potential of the cell-penetrating peptide may not be needed to enhance uptake.
Rights Statement: This version in OUR Archive is the author’s manuscript accepted for publication after peer-review. The published version is: Chiu JZS, Tucker IG, McLeod BJ and McDowell A (2015). Arginine-tagging of polymeric nanoparticles via histidine to improve cellular uptake. European Journal of Pharmaceutics and Biopharmaceutics 89: 48-55 This OUR Archive version is licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International https://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Poly(ethyl-cyanoacrylate) nanoparticles; polyarginine; MALDI-TOF; cationic; cell-penetrating peptides
Research Type: Journal Article
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