Cellular Delivery of Noncovalently-Associated Macromolecules by Cell-Penetrating Peptides


Cellular and nuclear delivery of biomolecules is limited by low membrane permeability. Cell-penetrating peptides (CPPs) can be covalently linked to cargos to improve cellular internalization. Our work indicates that arginine-rich CPPs are also able to interact with a variety of cargos, including DNA, RNA, proteins and nanomaterials, in a noncovalent manner and subsequently effect their delivery into cells. The advantages of noncovalent attachment in CPP-mediated transduction are multiple: ease of use, ease of production, and versatility with respect to both cargo composition and functional delivery (i.e., the cargo is not chemically modified). We have extended this approach to achieve simultaneous transduction of covalently and noncovalently associated complexes, opening a new method for delivering multiple types of cargos, including proteins, fluorescent nanomaterials, nucleic acid and others. These novel variations of CPP-mediated transport should be of broad utility in the transport of genes, small interfering RNAs, proteins and nanoparticles in biomedical research and therapeutic intervention.


Biological Sciences

Keywords and Phrases

DNA; Nanomaterial; Protein; RNA; Beta Galactosidase; Drug Carrier; Enhanced Green Fluorescent Protein; Nanoparticle; Proteoheparan Sulfate; Red Fluorescent Protein; Small Interfering RNA; Sulforhodamine B; Covalent Bond; DNA Immunization; Fluorescence Resonance Energy Transfer; Gene Therapy; Internalization; Macromolecule; Nonhuman; Nuclear Localization Signal; Pinocytosis; RNA Interference; Chemistry; Transport at the Cellular Level; Biocompatibility; Cell Membrane Transport; Confocal Microscopy; Cytotoxicity; Drug Delivery Device; Drug Penetration; Drug Protein Binding; Drug Transport; Flow Cytometry; Protein Transduction; Quantitative Structure Activity Relation; RNA Metabolism; Biological Transport; Cell-Penetrating Peptides; Drug Delivery Systems; Humans; Nanostructures; Proteins; Cellular Internalization; Macropinocytosis; Polyarginine; Protein Transduction Domain; Quantum Dots

International Standard Serial Number (ISSN)

1389-2010; 1873-4316

Document Type

Article - Journal

Document Version


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© 2014 Bentham Science Publishers, All rights reserved.

Publication Date

01 Jan 2014

PubMed ID