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EXP002002

Paper

A blood–brain barrier- and blood–brain tumor barrier-penetrating siRNA delivery system targeting gliomas for brain tumor immunotherapy (2024)

Peptide

Cholesterol-DP7-ACP-T7 (DAT) (dual-functional peptide on liposome)

Sequence: cholesterol-VQWRIRVAVIRK-ACP-HAIYPRH

RNA

siRNA (duplex, 21-mer with 3′ TT overhangs)

All experiment fields

Experiment Id EXP002002
Paper A blood–brain barrier- and blood–brain tumor barrier-penetrating siRNA delivery system targeting gli
Peptide Cholesterol-DP7-ACP-T7 (DAT) (dual-functional peptide on liposome)
Delivery Success Class yes
In Vivo Flag yes
Uptake Confirmed no
Label Confidence high
In Vitro Functional Effect
Endosomal Escape Evidence
Peptide Concentration DAT-modified LNP prepared with DAT 250 μg/mL; DOTAP 2 mg/mL.
Rna Concentration 1 mg/kg siRNA for biodistribution (cy5-siRNA) and for therapy (si slit2) via i.v. injection.
Mixing Ratio DAT-LNP:siRNA mass ratio 6:1 for complexation.
Formulation Format DAT-modified DOTAP:cholesterol liposome (DAT-LNP) electrostatically adsorbing siRNA
Formulation Components DOTAP:cholesterol (1:1 molar; DOTAP 2 mg/mL) liposome + DAT peptide (250 μg/mL for modification; dialysis) + siRNA (complexed at 6:1 mass ratio LNP:siRNA).
Size Nm 130.10
Zeta Mv
Model Scope in_vivo
Model Type in vivo
Cell Lines Or Primary Cells
Animal Model Orthotopic GL261 glioma model in female C57BL/6J mice (6–8 weeks); GL261 intracranial injection (1×10^5 cells/10 μL) day 0.
Administration Route Intravenous (i.v.) dosing every 2 days from day 7 to day 25 post-implantation; 1 mg/kg siRNA per dose.
Output Type In vivo functional delivery: tumor growth suppression and survival benefit in orthotopic glioma; histology (HE), proliferation/angiogenesis markers (Ki67, CD31), apoptosis (TUNEL), immune microenvironment activation.
Output Value DAT-LNP/si slit2: smaller tumor volume; increased apoptosis (TUNEL); reduced Ki67 and CD31; improved survival (reported 100% survival at day 27 vs controls).
Output Units
Output Notes Also increased mature DCs, M1 macrophages, and cytotoxic CD8+ IFN-γ+ T cells; decreased Tregs in tumor microenvironment.
Toxicity Notes No significant organ pathology (HE) and no significant liver/kidney blood chemistry changes vs PBS reported after i.v. dosing.
Curation Notes