Tumor Xenograft Model with siRNA Nanoparticle Treatment
Objective: Assess selective tumor uptake of ligand-targeted nanoparticles carrying VEGF R2-targeting siRNA, protein expression inhibition, and effects on angiogenesis and tumor growth in tumor-bearing mice
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Materials5
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Protocol Steps
Nanoparticle construction
Self-assembling nanoparticles with siRNA were constructed using polyethyleneimine (PEI) that is PEGylated with an Arg-Gly-Asp (RGD) peptide ligand attached at the distal end of the polyethylene glycol (PEG)
Note: The RGD peptide ligand targets tumor neovasculature expressing integrins
View evidence from paper
“Self-assembling nanoparticles with siRNA were constructed with polyethyleneimine (PEI) that is PEGylated with an Arg-Gly-Asp (RGD) peptide ligand attached at the distal end of the polyethylene glycol (PEG)”
In vitro cell delivery and activity assessment
Cell delivery and activity of PEGylated PEI was evaluated for siRNA sequence specificity and dependence on peptide ligand presence
Note: Activity could be competed by free peptide, demonstrating ligand-dependent targeting
View evidence from paper
“Cell delivery and activity of PEGylated PEI was found to be siRNA sequence specific and depend on the presence of peptide ligand and could be competed by free peptide”
Intravenous administration
Ligand-targeted sterically stabilized nanoparticles carrying VEGF R2-targeting siRNA were administered intravenously into tumor-bearing mice
Note: Administration route is intravenous
View evidence from paper
“Intravenous administration into tumor-bearing mice gave selective tumor uptake, siRNA sequence-specific inhibition of protein expression within the tumor”
Assessment of tumor uptake
Selective tumor uptake of nanoparticles was assessed following intravenous administration
Note: Uptake was selective to tumor tissue
View evidence from paper
“Intravenous administration into tumor-bearing mice gave selective tumor uptake”
Protein expression analysis
siRNA sequence-specific inhibition of protein expression within the tumor was evaluated
Note: Inhibition was sequence-specific
View evidence from paper
“siRNA sequence-specific inhibition of protein expression within the tumor”
Assessment of angiogenesis and tumor growth
Inhibition of both tumor angiogenesis and growth rate was evaluated following nanoparticle treatment
Note: Both angiogenesis and tumor growth rate were measured as outcome parameters
View evidence from paper
“inhibition of both tumor angiogenesis and growth rate”