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• W1972622966 abstract "The ability of cell-penetrating peptides (CPPs) to deliver a range of membrane-impermeable molecules into living cells makes them attractive potential vehicles for therapeutics. However, in vivo, the efficiency of CPP delivery to the cytosol remains unsatisfactory owing to endosomal entrapment and/or systemic toxicity, which severely restrict their bioavailability and efficacy in in vivo applications. In this study, we developed a series of novel chimeras consisting of various numbers of d- and l-arginine residues and investigated their cellular uptake behaviors and systemic toxicities. We demonstrated that the intracellular distribution, uptake efficiency, and systemic toxicity of these oligoarginines were all significantly affected by the number of d-arginine residues in the peptide sequence. We also found that a hybrid peptide, (rR)3R2, possessed low systemic toxicity, high uptake efficiency, and, remarkably, achieved efficient cytosolic delivery not only in cultured cells but also in living tissue cells in mice after intravenous injection, implying that this heterogeneous motif might have promising applications in the delivery of cargoes of small sizes directed to cytosolic targets in vivo. Our studies into the uptake mechanism of (rR)3R2 indicate that its cellular uptake was not affected by pharmacological or physical inhibitors of endocytosis but by the elimination of the membrane potential, suggesting that (rR)3R2 does not enter the cells via endocytosis but rather through direct membrane translocation driven by the membrane potential. The results here might provide useful guidelines for the design and application of CPPs in drug delivery." @default.
• W1972622966 created "2016-06-24" @default.
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• W1972622966 date "2012-09-01" @default.
• W1972622966 modified "2023-10-18" @default.
• W1972622966 title "Direct cytosolic delivery of cargoes in vivo by a chimera consisting of D- and L-arginine residues" @default.
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• W1972622966 doi "https://doi.org/10.1016/j.jconrel.2012.07.022" @default.
• W1972622966 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22824782" @default.
• W1972622966 hasPublicationYear "2012" @default.
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