title: Cargo-dependent cytotoxicity and delivery efficacy of cell-penetrating peptides: a comparative study.
abstract: The use of CPPs (cell-penetrating peptides) as delivery vectors for bioactive molecules has been an emerging field since 1994 when the first CPP, penetratin, was discovered. Since then, several CPPs, including the widely used Tat (transactivator of transcription) peptide, have been developed and utilized to translocate a wide range of compounds across the plasma membrane of cells both in vivo and in vitro. Although the field has emerged as a possible future candidate for drug delivery, little attention has been given to the potential toxic side effects that these peptides might exhibit in cargo delivery. Also, no comprehensive study has been performed to evaluate the relative efficacy of single CPPs to convey different cargos. Therefore we selected three of the major CPPs, penetratin, Tat and transportan 10, and evaluated their ability to deliver commonly used cargos, including fluoresceinyl moiety, double-stranded DNA and proteins (i.e. avidin and streptavidin), and studied their effect on membrane integrity and cell viability. Our results demonstrate the unfeasibility to use the translocation efficacy of fluorescein moiety as a gauge for CPP efficiency, since the delivery properties are dependent on the cargo used. Furthermore, and no less importantly, the toxicity of CPPs depends heavily on peptide concentration, cargo molecule and coupling strategy.
authors.affiliation: Department of Neurochemistry, Stockholm University, Stockholm 16091, Sweden.
authors.forename: Samir
authors.initials: S
authors.lastname: El-Andaloussi
authors.forename: Peter
authors.initials: P
authors.lastname: Järver
authors.forename: Henrik J
authors.initials: HJ
authors.lastname: Johansson
authors.forename: Ulo
authors.initials: U
authors.lastname: Langel
mesh_terms: D002352:Carrier Proteins / Q000627:therapeutic use / Q000633:toxicity; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides; D004247:DNA / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000009:adverse effects* / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions; D019004:Galanin / Q000627:therapeutic use / Q000633:toxicity; D015696:Gene Products, tat / Q000627:therapeutic use / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D010455:Peptides / Q000627:therapeutic use* / Q000633:toxicity; D011506:Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use / Q000633:toxicity; D014862:Wasp Venoms / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D015696:Gene Products, tat; D010455:Peptides; D011506:Proteins; D011993:Recombinant Fusion Proteins; D014862:Wasp Venoms; C110068:transportan; D019004:Galanin; D004247:DNA; C414409:penetratin