Synergistic effects of cell-penetrating peptide Tat and fusogenic peptide HA2-enhanced cellular internalization and gene transduction of organosilica nanoparticles.
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.
Research Center of Biomedical Engineering, Department of Biomaterials, College of Materials, Xiamen University, Xiamen, People's Republic of China.
She-fang
SF
Ye
Miao-miao
MM
Tian
Tian-xiao
TX
Wang
Lei
L
Ren
Dong
D
Wang
Li-hua
LH
Shen
Ting
T
Shang
D000818:Animals; D004247:DNA / Q000008:administration & dosage / Q000235:genetics*; D004357:Drug Synergism; D015696:Gene Products, tat / Q000493:pharmacokinetics*; D006367:HeLa Cells; D006801:Humans; D008422:Materials Testing; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D053769:Nanocapsules / Q000737:chemistry*; D009928:Organ Specificity; D017646:Organosilicon Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D010446:Peptide Fragments / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014161:Transduction, Genetic / Q000379:methods; D014162:Transfection / Q000379:methods*
D015696:Gene Products, tat; D053769:Nanocapsules; D017646:Organosilicon Compounds; D010446:Peptide Fragments; D004247:DNA