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EXP000731

Paper

Endosomolytic and Tumor-Penetrating Mesoporous Silica Nanoparticles for siRNA/miRNA Combination Cancer Therapy (2020)

Peptide

iRGD

Sequence: CRGDKGPDC

RNA

siRNA + miRNA mimic

All experiment fields

Experiment Id EXP000731
Paper Endosomolytic and Tumor-Penetrating Mesoporous Silica Nanoparticles for siRNA/miRNA Combination Canc
Peptide iRGD
Delivery Success Class yes
In Vivo Flag yes
Uptake Confirmed no
Label Confidence high
In Vitro Functional Effect
Endosomal Escape Evidence yes
Peptide Concentration
Rna Concentration In vivo dosing: 1 mg/kg siPlk1 + 1 mg/kg miR-200c (i.v.); ICG 720 µg/kg; twice weekly for 3 weeks
Mixing Ratio siRNA:miRNA=1:1 (w/w); MSN:RNAs=30:1 (w/w); lipids:MSN=2:1 (w/w); fixed ICG:RNA = 1 µg/mL : 200 nM (per RNA)
Formulation Format iRGD-modified lipid-coated mesoporous silica nanoparticle (iMSN) with ICG photosensitizer
Formulation Components NH2-MSN core (100–200 nm, 4 nm pores) adsorbing siRNA+miRNA; ICG loaded; lipid coat SPC/DSPE-mPEG/DSPE-PEG-DBCO (2:2:1 w/w/w); iRGD (azido) click-conjugated (DSPE-PEG-DBCO:iRGD 1:1 molar)
Size Nm 100.00
Zeta Mv -19.00
Model Scope in_vivo
Model Type in vivo (mouse orthotopic metastatic breast cancer)
Cell Lines Or Primary Cells
Animal Model Immunocompromised female NCG mice with orthotopic MDA-MB-231.Luc tumors (mammary fat pad); metastasis monitored by IVIS
Administration Route Intravenous (tail vein) + 808 nm laser irradiation of primary tumor (5 min, ~4 h post-dose; some groups −light)
Output Type in vivo therapeutic efficacy
Output Value Significant primary tumor growth suppression/regression and marked reduction of metastasis for iMSN/siPlk1+miR-200c+ICG with light
Output Units
Output Notes Biodistribution: sustained tumor accumulation of ICG signal and tumor section fluorescence (FAM-siRNA/ICG) vs controls; IHC showed downregulation of Plk1 and ZEB1 in tumors in treated group; lung metastasis markedly reduced with +light.
Toxicity Notes No significant weight loss; blood counts/biochemistry indicated no toxic effects (reported).
Curation Notes