iRGD-guided Tumor-penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer (2018)
iRGD TPN (PEGylated) therapeutic dosing [15:2.5:1 pTP-TAM-iRGD:pTP-PEG(5k)-iRGD:siKras]
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 | EXP001877 |
|---|---|
| Paper | iRGD-guided Tumor-penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer |
| Peptide | iRGD TPN (PEGylated) therapeutic dosing [15:2.5:1 pTP-TAM-iRGD:pTP-PEG(5k)-iRGD:siKras] |
| 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 | NCR/nude mice bearing bilateral flank KP D8-175 luciferized KPC-derived PDAC allografts |
| Administration Route | Intravenous dosing 0.5 mg/kg siRNA on days 1,4,7,11,15,18,21,25,30,35 (in D5W) |
| Output Type | In vivo therapeutic efficacy: tumor growth delay / survival surrogate |
| Output Value | Anti-Kras siRNA TPNs significantly slowed tumor growth vs saline and siNC controls; extended survival proxy (tumor burden threshold) |
| Output Units | |
| Output Notes | Two-way ANOVA significant at ~6 weeks; TAMRA peptide staining used as proxy for intracellular delivery in tumors. |
| Toxicity Notes | |
| Curation Notes |