Targeted melanoma therapy: High-efficiency siRNA delivery with R8-PEI dissolvable microneedles (2025)
R8-PEI (octaarginine-modified PEI 25k)
Sequence: R8 = (Arg)8 (Fmoc-[R(Pbf)]8-COOH precursor); conjugated to PEI via amide bond
| Experiment Id | EXP001751 |
|---|---|
| Paper | Targeted melanoma therapy: High-efficiency siRNA delivery with R8-PEI dissolvable microneedles |
| Peptide | R8-PEI (octaarginine-modified PEI 25k) |
| Delivery Success Class | no |
| In Vivo Flag | no |
| Uptake Confirmed | yes |
| Label Confidence | high |
| In Vitro Functional Effect | yes |
| Endosomal Escape Evidence | yes |
| Peptide Concentration | R8-PEI/siRNA complexes dosed by siRNA concentration (e.g., 60 nM for uptake/migration; 150 nM+ for proliferation inhibition). |
| Rna Concentration | Typically 60 nM (uptake/migration/qPCR); proliferation assays used increasing siRNA concentrations (not all enumerated in text). |
| Mixing Ratio | N/P = 40:1 (chosen for subsequent experiments; complete siRNA binding from N/P ≥5). |
| Formulation Format | Polyplex (siRNA@R8-PEI), optionally loaded into dissolvable microneedles (DMNs) for transdermal delivery |
| Formulation Components | siRNA complexed with R8-PEI by mixing at set N/P ratio and incubating 30 min RT; DMNs prepared with polymer blend (PVP, CMC-Na, HPMC E15, PVA1788, HA) dissolved in siRNA@R8-PEI solution and cast into PDMS molds. |
| Size Nm | 170.37 |
| Zeta Mv | |
| Model Scope | in_vitro |
| Model Type | in vitro |
| Cell Lines Or Primary Cells | A375 human melanoma cells; HaCat normal epidermal cells for cytotoxicity |
| Animal Model | |
| Administration Route | |
| Output Type | in vitro uptake, endosomal escape, and gene silencing/phenotype |
| Output Value | BRAF mRNA reduced by ~74% (qPCR) vs NC; strong proliferation inhibition (≈90% at higher doses per abstract); migration reduced (scratch and transwell). |
| Output Units | |
| Output Notes | Uptake quantified by flow cytometry (siRNA-Cy3@R8-PEI) and microscopy; uptake inhibited by chlorpromazine and amiloride indicating mainly clathrin-mediated endocytosis. Lysosomal escape shown by separation of Cy3-siRNA from LysoTracker-Green after 2–8 h. |
| Toxicity Notes | CCK-8: vector cytotoxicity low; survival >80% at highest tested concentration in A375 and HaCat. |
| Curation Notes |