iRGD-guided Tumor-penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer (2018)
iRGD TPN (PEGylated) [pTP-iRGD + pTP-PEG-iRGD]
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 | EXP001875 |
|---|---|
| Paper | iRGD-guided Tumor-penetrating Nanocomplexes for Therapeutic siRNA Delivery to Pancreatic Cancer |
| Peptide | iRGD TPN (PEGylated) [pTP-iRGD + pTP-PEG-iRGD] |
| Delivery Success Class | no |
| In Vivo Flag | no |
| Uptake Confirmed | yes |
| Label Confidence | high |
| In Vitro Functional Effect | yes |
| 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 | Peptide:siRNA typically ~10:1 (stoichiometric); PEGylated examples 15:2.5:1 or 15:7.5:1 (pTP-iRGD:pTP-PEG-iRGD:siRNA) in vivo |
| 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_vitro |
| Model Type | in vitro |
| Cell Lines Or Primary Cells | KP B22 (KPC-derived, luciferized) and PANC-1 / MIA PaCa-2 human PDAC lines |
| Animal Model | |
| Administration Route | |
| Output Type | In vitro functional RNA effect: KRAS mRNA (qPCR) and protein (WB) knockdown |
| Output Value | ~90% Kras mRNA knockdown in B22 at 48h; >95% KRAS mRNA knockdown in PANC-1; PEGylated and non-PEGylated similar potency in MIA PaCa-2/PANC-1 |
| Output Units | |
| Output Notes | TPNs formed at ~10:1 peptide:siRNA for in vitro function; typical siRNA concentration 100 nM; seed-matched controls used. |
| Toxicity Notes | |
| Curation Notes |