Nuclear localization of HIV-1 tat functionalized gold nanoparticles.
The impermeable nature of the cell plasma membrane limits the therapeutic uses of many macromolecules and there is therefore a growing effort to circumvent this problem by designing strategies for targeted intracellular delivery. During the last decade several cell penetrating peptides, such as the HIV-1 tat peptide, have been shown to traverse the cell membrane, where integral protein transduction domains (PTDs) are responsible for their cellular uptake, and to reach the nucleus while retaining biological activity. It has since been discovered that PTDs can enable the cellular delivery of conjugated biomolecules and even nanoparticles, but nuclear delivery has remained problematic. This present study focuses on the development of water soluble, biocompatible gold nanoparticles of differing size functionalized with the HIV-1 tat PTD with the aim of producing nuclear targeting agents. The particles were subsequently tested in vitro with a human fibroblast cell line, with results demonstrating successful nanoparticle transfer across the plasma membrane, with 5 nm particles achieving nuclear entry while larger 30 nm particles are retained in the cytoplasm, suggesting entry is blocked via nuclear pores dimensions.
Berry
C C
CC
Centre for Cell Engineering, Institute of Biomedical and Life Sciences, University of Glasgow, UK. Catherine.berry@bio.gla.ac.uk
de la Fuente
J M
JM
Mullin
M
M
Chu
S Wai Ling
SW
Curtis
A S G
AS
D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000378:metabolism / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism; D006046:Gold; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D053758:Nanoparticles; D036103:Nanotechnology; D019913:Nuclear Localization Signals; D021381:Protein Transport; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*
D019913:Nuclear Localization Signals; D054322:tat Gene Products, Human Immunodeficiency Virus; D006046:Gold