NDLI: Tat Peptide Is Capable of Importing Large Nanoparticles Across Nuclear Membrane in Digitonin Permeabilized Cells

Content Provider	Springer Nature Link
Author	Nitin, Nitin LaConte, Leslie Rhee, Won Jong Bao, Gang
Copyright Year	2009
Abstract	Understanding the capabilities and limitations of nuclear import is crucial to efficient delivery of macromolecules and nanoparticles for diagnosis and targeted therapy of diseases. Here we report the Tat peptide-mediated import of different cargos into cell nucleus, including dye-labeled streptavidin protein, 43 and 90 nm fluorescent beads, as well as ~20 nm quantum dots for kinetic measurements. Our results revealed significant differences between Tat- and NLS-mediated nuclear import: unlike delivery with the NLS, Tat peptide-based delivery is not inhibited by WGA blockage nor does it require ATP. Surprisingly, Tat peptide was able to import 90 nm beads into the nuclei of digitonin-permeabilized cells, suggesting that its interaction with the nuclear envelope follows a mechanism different from that of NLS. The import kinetics was quantified using Tat peptide-conjugated QDs, yielding a kinetic constant of 0.0085 s−1. Taken together, our results suggest that, compared with NLS, Tat peptide-mediated nuclear import is faster, follows a different pathway, and is capable of importing large nanoparticles. These results have significant implications for the development of new approaches for delivery of cargo into the nuclei of living cells.
Starting Page	2018
Ending Page	2027
Page Count	10
File Format	PDF
ISSN	00906964
Journal	Annals of Biomedical Engineering
Volume Number	37
Issue Number	10
e-ISSN	15739686
Language	English
Publisher	Springer US
Publisher Date	2009-08-06
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Nuclear delivery Nanoparticles Nuclear localizing sequence Tat Biochemistry Mechanics Biophysics and Biological Physics Biomedical Engineering Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Biomedical Engineering

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