Journal
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
Volume 14, Issue -, Pages 1378-1388Publisher
BEILSTEIN-INSTITUT
DOI: 10.3762/bjoc.14.116
Keywords
anticancer drugs; cell nuclei; cell-penetrating peptides; nucleoli; subcellular targeting
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Funding
- Jurgen-Manchot Stiftung
- European Union within the MSCA-ITN-2014-ETN MAGICBULLET [642004]
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Within this study, we report about the design and biological characterization of novel cell-penetrating peptides (CPPs) with selective suborganelle-targeting properties. The nuclear localization sequence N50, as well as the nucleoli-targeting sequence NrTP, respectively, were fused to a shortened version of the cell-penetrating peptide sC18. We examined cellular uptake, subcellular fate and cytotoxicity of these novel peptides, N50-sC18* and NrTP-sC18*, and found that they are nontoxic up to a concentration of 50 or 100 mu M depending on the cell lines used. Moreover, detailed cellular uptake studies revealed that both peptides enter cells via energy-independent uptake, although endocytotic processes cannot completely excluded. However, initial drug delivery studies demonstrated the high versatility of these new peptides as efficient transport vectors targeting specifically nuclei and nucleoli. In future, they could be further explored as parts of newly created peptide-drug conjugates.
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