Gold nanoparticle-DNA aptamer composites as a universal carrier for in vivo delivery of biologically functional proteins.

Abstract

Although the delivery of biologically functional protein(s) into mammalian cells could be of tremendous value to biomedical research, the development of such technology has been hindered by the lack of a safe and effective delivery method. Here, we present a simple, efficient, and versatile gold nanoparticle-DNA aptamer conjugate (AuNP-Apt)-based system, with nanoblock-like properties, that allows any recombinant protein to be loaded without additional modifications and delivered into mammalian living systems. AuNP-Apt-based protein delivery system was able to deliver various proteins into variety of cell types in vitro without showing cytotoxicity. This AuNP-Apt system was also effective for the local and systemic targeted delivery of proteins in vivo. A local injection of the AuNP-Apt loaded with the apoptosis-inducing BIM protein efficiently inhibited the growth of xenograft tumors in mice. Furthermore, an intravenous injection of AuNP-Apt loaded with both epidermal growth factor (EGF) and BIM resulted in the targeted delivery of BIM into a xenograft tumor derived from EGF receptor-overexpressing cancer cells with no detectable systemic toxicity. Our findings show that this system can serve as an innovative platform for the development of protein-based biomedical applications.

• Authors: Sang-Mi Ryou, Ji-Hyun Yeom, Hyo Jung Kang, Miae Won, Jin-Sik Kim, Boeun Lee, Maeng-Je Seong, Nam-Chul Ha, Jeehyeon Bae, Kangseok Lee
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 196 Pg. 287-94 (Dec 28 2014) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 25450403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• Aptamers, Nucleotide
• Bcl-2-Like Protein 11
• Bcl2l11 protein, mouse
• Bcl2l11 protein, rat
• Drug Carriers
• Membrane Proteins
• Proteins
• Proto-Oncogene Proteins
• Recombinant Proteins
• Gold

Topics

• Animals
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (administration & dosage, pharmacology)
• Aptamers, Nucleotide (chemistry)
• Bcl-2-Like Protein 11
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Carriers
• Drug Delivery Systems
• Gold
• Membrane Proteins (administration & dosage, pharmacology)
• Metal Nanoparticles (chemistry)
• Mice
• Mice, Inbred BALB C
• Proteins (administration & dosage, therapeutic use)
• Proto-Oncogene Proteins (administration & dosage, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (administration & dosage, therapeutic use)
• Xenograft Model Antitumor Assays