Journal
BIOMATERIALS
Volume 35, Issue 24, Pages 6454-6461Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.04.014
Keywords
Protein delivery; Nucleic acid; Oligonucleotide; Intracellular delivery; Nanoparticles; Lipid
Funding
- National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), as a Program of Excellence in Nanotechnology (PEN) Award [HHSN268201000045C]
- NIH [R01-EB000244-27, 5-R01-CA132091-04]
- NSF
- Juvenile Diabetes Research Foundation International grant [17-2007-1063]
- Congressionally Directed Medical Research Programs (CDMRP), Department of Defense (DOD), postdoctoral fellowship award [W81XWH-13-1-0215]
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Intracellular protein delivery has potential biotechnological and therapeutic application, but remains technically challenging. In contrast, a plethora of nucleic acid carriers have been developed, with lipid-based nanoparticles (LNPs) among the most clinically advanced reagents for oligonucleotide delivery. Here, we validate the hypothesis that oligonucleotides can serve as packaging materials to facilitate protein entrapment within and intracellular delivery by LNPs. Using two distinct model proteins, horseradish peroxidase and NeutrAvidin, we demonstrate that LNPs can yield efficient intracellular protein delivery in vitro when one or more oligonucleotides have been conjugated to the protein cargo. Moreover, in experiments with NeutrAvidin in vivo, we show that oligonucleotide conjugation significantly enhances LNP-mediated protein uptake within various spleen cell populations, suggesting that this approach may be particularly suitable for improved delivery of protein-based vaccines to antigen-presenting cells. (C) 2014 Elsevier Ltd. All rights reserved.
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