Abstract

Cell-penetrating peptides (CPPs) can traverse cellular membranes and deliver biologically active molecules into cells. In this study, we demonstrate that CPPs comprised of nona-arginine (R9) and a penetration accelerating peptide sequence (Pas) that facilitates escape from endocytic lysosomes, denoted as PR9, greatly enhance the delivery of noncovalently associated quantum dots (QDs) into human A549 cells. Mechanistic studies, intracellular trafficking analysis and a functional gene assay reveal that endocytosis is the main route for intracellular delivery of PR9/QD complexes. Endocytic trafficking of PR9/QD complexes was monitored using both confocal and transmission electron microscopy (TEM). Zeta-potential and size analyses indicate the importance of electrostatic forces in the interaction of PR9/QD complexes with plasma membranes. Circular dichroism (CD) spectroscopy reveals that the secondary structural elements of PR9 have similar conformations in aqueous buffer at pH 7 and 5. This study of nontoxic PR9 provides a basis for the design of optimized cargo delivery that allows escape from endocytic vesicles.

Department(s)

Biological Sciences

Keywords and Phrases

Arginine; Buffer; Nonaarginine; Unclassified Drug; Actin; Arginine; Amino Acid Sequence; Aqueous Solution; Cell Line; Cell Membrane; Chemical Interaction; Circular Dichroism; Confocal Microscopy; Controlled Study; Endocytosis; Endosome; Genetic Analysis; Human Cell; Internalization; Intracellular Transport; Particle Size; pH; Protein Conformation; Protein Secondary Structure; Static Electricity; Transmission Electron Microscopy; Zeta Potential; A-549 Cell Line; Chemistry; Intracellular Space; Kinetics; Metabolism; Protein Transport; A549 Cells; Actins; Cell-Penetrating Peptides; Drug Carriers; Humans; Lysosomes; Nanoparticles; Quantum Dots

International Standard Serial Number (ISSN)

1932-6203

Document Type

Article - Journal

Document Version

Final Version

File Type

text

Language(s)

English

Rights

© 2013 Public Library of Science, All rights reserved.

Creative Commons Licensing

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.

PubMed ID

23840594

Included in

Biology Commons

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