Synergistic effects of cell-penetrating peptide Tat and fusogenic peptide HA2-enhanced cellular internalization and gene transduction of organosilica nanoparticles
Abstract
The nonviral gene delivery system is an attractive alternative to cancer therapy. A new kind of gelatin-silica nanoparticles (GSNPs) was developed through a two-step sol–gel procedure. To improve the transfection efficacy, GSNPs modified with different fusion peptides (Tat, HA2, R8, Tat/HA2, and Tat/R8) were prepared for particle size, zeta potential, cellular uptake, hemolysis activity at physiological pH (7.0) or acidic pH (5.0), and condensation of plasmid DNA. The results suggest that the sizes and zeta potentials of GS-peptide conjugates were 147 – 161 nm and 19 – 33 mV, respectively; GS-peptide conjugates exhibited low cytotoxicity; the plasmid DNA was readily entrapped at a GS-peptide/pDNA weight ratio of 50 – 200. The in vitro and in vivo studies demonstrated that the synergistic effects of cell-penetrating peptide Tat and fusogenic peptide HA2 could promote the efficient cellular internalization, endosome escape, and nucleus targeting, hence delivering the therapeutic nucleic acid efficiently.
Graphical Abstract
The synergistic effects of cell-penetrating peptide Tat and fusogenic peptide HA2 could promote the efficient cellular internalization, endosome escape, and nuclear targeting of the therapeutics' nucleic acid, hence delivering genes efficiently.
Key words: Cell penetrating peptides, Fusogenic peptides, Nucleic acid delivery, Non-viral vectors
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No conflict of interest was reported by the authors of this article.
This work was funded by the National Basic Research Program of China (973 Program) (2010CB732402) and the National Natural Science Foundation of China (30970733, 30901175, 81171448).
PII: S1549-9634(11)00376-5
doi:10.1016/j.nano.2011.10.003
© 2011 Elsevier Inc. All rights reserved.
