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 | EXP001752 |
|---|---|
| Paper | Targeted melanoma therapy: High-efficiency siRNA delivery with R8-PEI dissolvable microneedles |
| Peptide | R8-PEI (octaarginine-modified PEI 25k) |
| Delivery Success Class | yes |
| In Vivo Flag | yes |
| Uptake Confirmed | yes |
| Label Confidence | high |
| In Vitro Functional Effect | |
| Endosomal Escape Evidence | |
| Peptide Concentration | Delivered as siRNA@R8-PEI/DMNs (dose referenced by siRNA: 1 mg/kg); DMN needle content ~93.92%. |
| Rna Concentration | siRNA dose 1 mg/kg (percutaneous DMNs); negative control siNC microneedle 1 mg/kg. |
| 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_vivo |
| Model Type | in vivo |
| Cell Lines Or Primary Cells | |
| Animal Model | BALB/c nude mice bearing A375 melanoma xenograft (subcutaneous 5×10^6 cells; ~100 mm^3 at day 6) |
| Administration Route | Percutaneous transdermal delivery via dissolvable microneedles applied 10 min every 2 days (siRNA dose 1 mg/kg) |
| Output Type | in vivo tumor inhibition + in vivo target knockdown |
| Output Value | Volumetric tumor inhibition ~67.15% and tumor weight inhibition ~75.50% vs NC; tumor BRAF mRNA reduced to ~72.8% of NC (qPCR) with decreased BRAF and Ki67 staining and increased TUNEL signal. |
| Output Units | |
| Output Notes | Four groups: siNC MN, verofenib (oral, 30 mg/kg), siRNA@PEI/DMNs, siRNA@R8-PEI/DMNs. Tumor/organ histology assessed (H&E, Ki67, BRAF IHC; TUNEL). |
| Toxicity Notes | Body weight monitored; H&E of major organs reported; microneedle puncture sites healed within minutes with no erythema/swelling; no major organ pathology described. |
| Curation Notes |