Nanoparticle-Mediated Cytoplasmic Delivery of Proteins To Target Cellular Machinery
- 4 March 2010
- journal article
- Published by American Chemical Society (ACS) in ACS Nano
- Vol. 4 (3), 1493-1500
- https://doi.org/10.1021/nn901586e
Abstract
Despite recent advances in nanomaterial-based delivery systems, their applicability as carriers of cargo, especially proteins for targeting cellular components and manipulating cell function, is not well-understood. Herein, we demonstrate the ability of hydrophobic silica nanoparticles to deliver proteins, including enzymes and antibodies, to a diverse set of mammalian cells, including human cancer cells and rat stem cells, while preserving the activity of the biomolecule post-delivery. Specifically, we have explored the delivery and cytosolic activity of hydrophobically functionalized silica nanoparticle−protein conjugates in a human breast cancer cell line (MCF-7) and rat neural stem cells (NSCs) and elucidated the mechanism of cytosolic transport. Importantly, the proteins were delivered to the cytosol without extended entrapment in the endosomes, which facilitated the retention of biological activity of the delivered proteins. As a result, delivery of ribonuclease A (RNase A) and the antibody to phospho-Akt (pAkt) resulted in the initiation of cell death. Delivery of control protein conjugates (e.g., those containing green fluorescent protein or goat antirabbit IgG) resulted in minimal cell death, indicating that the carrier-mediated toxicity was low. The results presented here provide insight into the design of nanomaterials as protein carriers that enable control of cell function.Keywords
This publication has 31 references indexed in Scilit:
- RNA Interference in Mammalian Cell SystemsPublished by Springer Science and Business Media LLC ,2008
- Protein therapeutics: a summary and pharmacological classificationNature Reviews Drug Discovery, 2008
- Mesoporous Silica Nanoparticles for Intracellular Delivery of Membrane-Impermeable ProteinsJournal of the American Chemical Society, 2007
- RNAi-mediated knockdown of target genes: a promising strategy for pancreatic cancer researchCancer Gene Therapy, 2007
- Intracellular delivery of proteins into mammalian living cells by polyethylenimine-cationizationJournal of Bioscience and Bioengineering, 2005
- Nanotube Molecular Transporters: Internalization of Carbon Nanotube−Protein Conjugates into Mammalian CellsJournal of the American Chemical Society, 2004
- Tumor Cell Killing Enabled by Listeriolysin O-liposome-mediated Delivery of the Protein Toxin GeloninJournal of Biological Chemistry, 2003
- The phosphatidylinositol 3-Kinase–AKT pathway in human cancerNature Reviews Cancer, 2002
- Protein transduction: an alternative to genetic intervention?Gene Therapy, 2001
- In vivo protein transduction: intracellular delivery of biologically active proteins, compounds and DNATrends in Pharmacological Sciences, 2000