iRGD-guided Tumor-penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer (2018)
iRGD TPN (PEGylated) [15:2.5:1 pTP-TAM-iRGD:pTP-PEG(5k)-iRGD:siRNA]
Sequence: Palmitoyl-transportan-iRGD (pTP-TAMRA-iRGD): CH3(CH)15-[GWTLNSAGYLLGKINLKALAALAKKIL-GGK(TAMRA)GGCRGDKGPDC] (Cys-Cys bridge) ; Palmitoyl-transportan-PEG(5kDa)-iRGD (pTP-PEG-iRGD): (CH3(CH)15-[GWTLNSAGYLLGKINLKALAALAKKILC]-S-S-PEG(5kDa)-X-[GGGCRGDKGPDC] (Cys-Cys bridge))
| Experiment Id | EXP001876 |
|---|---|
| Paper | iRGD-guided Tumor-penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer |
| Peptide | iRGD TPN (PEGylated) [15:2.5:1 pTP-TAM-iRGD:pTP-PEG(5k)-iRGD:siRNA] |
| Delivery Success Class | yes |
| In Vivo Flag | yes |
| Uptake Confirmed | yes |
| Label Confidence | high |
| In Vitro Functional Effect | |
| Endosomal Escape Evidence | |
| Peptide Concentration | TPNs formed by mixing peptide and siRNA solutions; in vitro dosing at 100 nM siRNA (typical); in vivo dose 0.5 mg/kg siRNA for key PDAC studies |
| Rna Concentration | In vitro: 100 nM siRNA (typical transfection); In vivo: 0.5 mg/kg siRNA per dose (therapeutic and knockdown studies) |
| Mixing Ratio | 15:2.5:1 (pTP-TAM-iRGD : pTP-PEG(5k)-iRGD : siRNA) |
| Formulation Format | Self-assembled tandem peptide/siRNA nanocomplex (TPN), with optional PEG-peptide component |
| Formulation Components | Tandem peptide core: palmitoyl-transportan-iRGD; PEGylated formulation includes pTP-PEG-iRGD as third component |
| Size Nm | |
| Zeta Mv | |
| Model Scope | in_vivo |
| Model Type | in vivo |
| Cell Lines Or Primary Cells | |
| Animal Model | Immunocompetent KPC GEMM (Pdx1-Cre; KrasLSL-G12D/+; Trp53fl/fl) pancreatic tumors |
| Administration Route | Intravenous injection (0.5 mg/kg siRNA); tumors harvested 48 h post-dose for qRT-PCR |
| Output Type | In vivo functional RNA effect: tumor KRAS mRNA knockdown |
| Output Value | Significant Kras mRNA reduction in KPC tumors at 48 h after single i.v. dose vs controls/siNC |
| Output Units | |
| Output Notes | Demonstrates functional in vivo delivery in autochthonous PDAC model. |
| Toxicity Notes | |
| Curation Notes |