Abstract

Cell-penetrating peptides (CPPs) comprised of basic amino residues are able to cross cytoplasmic membranes and are able to deliver biologically active molecules inside cells. However, CPP/cargo entrapment in endosome limits biomedical utility as cargoes are destroyed in the acidic environment. In this study, we demonstrate protein transduction of a novel CPP comprised of an INF7 fusion peptide and nona-arginine (designated IR9). IR9 noncovalently interacts with quantum dots (QDs) and DNAs to form stable IR9/QD and IR9/DNA complexes which are capable of entering human A549 cells. Zeta-potentials were a better predictor of transduction efficiency than gel shift analysis, emphasizing the importance of electrostatic interactions of CPP/cargo complexes with plasma membranes. Mechanistic studies revealed that IR9, IR9/QD and IR9/DNA complexes may enter cells by endocytosis. Further, IR9, IR9/QD and IR9/DNA complexes were not cytotoxic at concentrations below 30, 5 and 20.1 μM, respectively. Without labor intensive production of fusion proteins from prokaryotes, these results indicate that IR9 could be a safe carrier of genes and drugs in biomedical applications.

Department(s)

Biological Sciences

Keywords and Phrases

DNA; Hybrid Protein; IR9 Peptide; Unclassified Drug; Cell Mediated Cytotoxicity; Cellular Distribution; Concentration (Parameters); Controlled Study; Endocytosis; Flow Cytometry; Gel Mobility Shift Assay; Gene Delivery System; Human Cell; Internalization; Molecular Interaction; Nanopharmaceutics; Signal Transduction; Static Electricity; Zeta Potential; Cell Death; Cell-Penetrating Peptides; Drug Delivery Systems; Humans; Intracellular Space; Microscopy, Confocal; Microscopy, Fluorescence; Nanoparticles; Plasmids; Quantum Dots; Prokaryota

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 4.0 License.

PubMed ID

23724035

Included in

Biology Commons

Share

 
COinS