Analysis of in vitro toxicity of five cell-penetrating peptides by metabolic profiling
2009 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 265, no 3, 87-95 p.Article in journal (Refereed) Published
Cell-penetrating peptides (CPPs) are promising candidates for safe and efficient delivery vectors for a wide range of cargoes. However, any compound that is internalized into cells may affect the cell homeostasis. The plethora of possible biological responses makes large scale “omics” studies appealing approaches for hunting any unsuspected side-effects and evaluate the toxicity of drug candidates. Here we have compared the alterations in cytosolic metabolome of CHO cells caused by five representatives of the most common CPPs: transportan (TP), penetratin (pAntp), HIV Tat derived peptide (pTat), nonaarginine (R9) and model amphipathic peptide (MAP). Analysis was done by liquid chromatography–mass spectrometry techniques, principal component analysis and heatmap displays. Results showed that the intracellular metabolome was the most affected by TP followed by pTat and MAP. Only minor changes could be associated with pAntp or R9 treatment. The cells could recover from a treatment with 5 μM TP, but no recovery was observed at higher concentration. Both metabolomic and control experiments showed that TP affected cellular redox potential, depleted energy and the pools of purines and pyrimidines. In conclusion, we have performed a metabolomic analysis comparing the safety of cell-penetrating peptides and demonstrate the toxicity of one of them.
Place, publisher, year, edition, pages
2009. Vol. 265, no 3, 87-95 p.
Metabolomics, Cell-penetrating peptides, Cytotoxicity, Side-effects, Delivery vehicles
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Neurosciences
Research subject Neurochemistry with Molecular Neurobiology
IdentifiersURN: urn:nbn:se:su:diva-32176DOI: 10.1016/j.tox.2009.09.016ISI: 000272567700003OAI: oai:DiVA.org:su-32176DiVA: diva2:279684