Browsing by Author "Ülo Langel"

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    Applications of cell-penetrating peptides for tumor targeting and future cancer therapies
    (2012-07-12) Jakob Regberg; Artita Srimanee; Ülo Langel; Stockholms universitet; Mahidol University
    Cell-penetrating peptides provide a highly promising strategy for intracellular drug delivery. One relevant clinical application of cell-penetrating peptides is cancer therapeutics. Peptide based delivery could increase the uptake of drugs in tumor cells and thereby increase the efficacy of the treatment, either of conventional small molecular drugs or oligonucleotide based therapeutics. This review is focused on the cancer applications of cell penetrating peptides as delivery systems; different aspects of drug loading, cargoes and delivery are discussed together with methods for targeted delivery, activatable cell-penetrating peptides and transducible agents coupled to cell-penetrating peptides. © 2012 by the authors; licensee MDPI, Basel, Switzerland.
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    Peptide-based delivery of oligonucleotides across blood-brain barrier model
    (2014-01-01) Artita Srimanee; Jakob Regberg; Mattias Hallbrink; Kaido Kurrikoff; Kadi Liis Veiman; Opa Vajragupta; Ülo Langel; Mahidol University; Stockholms universitet; University of Tartu
    Delivery of pharmaceutical agents across a blood-brain barrier (BBB) is a challenge for brain cancer therapy. In this study, an in vitro BBB model was utilized to study the delivery of oligonucleotides across brain endothelial cells targeting to glioma cells in a Transwell™ setup. A series of novel peptides were synthesized by covalent conjugation of cell-penetrating peptides with targeting peptides for delivery of gene-based therapeutics. These peptides were screened for passage across the Transwell™ and we found the most efficient peptide PepFect32 from originating PepFect 14 coupled with the targeting peptide angiopep-2. PepFect32/pDNA nanocomplexes exhibited high transcytosis across the BBB in vitro model and the highest transfection efficiency to glioma cells. In conclusion, PepFect32 revealed the most efficient peptide-based vector for pDNA delivery across in vitro BBB model. © 2013 Springer Science+Business Media.
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    Rational design of a series of novel amphipathic cell-penetrating peptides
    (2014-04-10) Jakob Regberg; Artita Srimanee; Mikael Erlandsson; Rannar Sillard; Dimitar A. Dobchev; Mati Karelson; Ülo Langel; Stockholms universitet; Mahidol University; University of Tartu; Tallinn University of Technology
    A series of novel, amphipathic cell-penetrating peptides was developed based on a combination of the model amphipathic peptide sequence and modifications based on the strategies developed for PepFect and NickFect peptides. The aim was to study the role of amphipathicity for peptide uptake and to investigate if the modifications developed for PepFect peptides could be used to improve the uptake of another class of cell-penetrating peptides. The peptides were synthesized by solid phase peptide synthesis and characterized by circular dichroism spectroscopy. Non-covalent peptide-plasmid complexes were formed by co-incubation of the peptides and plasmids in water solution. The complexes were characterized by dynamic light scattering and cellular uptake of the complexes was studied in a luciferase-based plasmid transfection assay. A quantitative structure-activity relationship (QSAR) model of cellular uptake was developed using descriptors including hydrogen bonding, peptide charge and positions of nitrogen atoms. The peptides were found to be non-toxic and could efficiently transfect cells with plasmid DNA. Cellular uptake data was correlated to QSAR predictions and the predicted biological effects obtained from the model correlated well with experimental data. The QSAR model could improve the understanding of structural requirements for cell penetration, or could potentially be used to predict more efficient cell-penetrating peptides. © 2014 Elsevier B.V.