Journal article
Targeted Intracellular Delivery of Proteins with Spatial and Temporal Control
Molecular pharmaceutics, v 12(2), pp 600-609
02 Feb 2015
PMID: 25490248
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
While a host of methods exist to deliver genetic materials or small molecules to cells, very few are available for protein delivery to the cytosol. We describe a modular, light-activated nanocarrier that transports proteins into cells by receptor-mediated endocytosis and delivers the cargo to the cytosol by light triggered endosomal escape. The platform is based on hollow gold nanoshells (HGN) with polyhistidine tagged proteins attached through an avidity-enhanced, nickel chelation linking layer; here, we used green fluorescent protein (GFP) as a model deliverable cargo. Endosomal uptake of the GFP loaded nanocarrier was mediated by a C-end Rule (CendR) internalizing peptide fused to the GFP. Focused femtosecond pulsed-laser excitation triggered protein release from the nanocarrier and endosome disruption, and the released protein was capable of targeting the nucleoli, a model intracellular organelle. We further demonstrate the generality of the approach by loading and releasing Sox2 and p53. This method for targeting of individual cells, with resolution similar to microinjection, provides spatial and temporal control over protein delivery.
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Details
- Title
- Targeted Intracellular Delivery of Proteins with Spatial and Temporal Control
- Creators
- Demosthenes P. Morales - University of California, Santa BarbaraGary B. Braun - Sanford Burnham Prebys Medical Discovery InstituteAlessia Pallaoro - University of California, Santa BarbaraRenwei Chen - Sanford Burnham Prebys Medical Discovery InstituteXiao Huang - University of California, Santa BarbaraJoseph A. Zasadzinski - University of MinnesotaNorbert O. Reich - University of California, Santa Barbara
- Publication Details
- Molecular pharmaceutics, v 12(2), pp 600-609
- Publisher
- ACS Publications
- Number of pages
- 10
- Grant note
- R01EB012637 / NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB) 1S10RR022585-01A1; R01 CA 152327; T32 CA 121949 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Cancer Center of Santa Barbara NSF-OISE-0968399 / NSF; National Science Foundation (NSF) R01CA152327 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) S10RR022585 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) R01 EB012637 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 0968399 / Office Of The Director; National Science Foundation (NSF); NSF - Office of the Director (OD)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000348886900031
- Scopus ID
- 2-s2.0-84961289006
- Other Identifier
- 991022130636304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Medicine, Research & Experimental
- Pharmacology & Pharmacy