Hybrid Liposome-U87MG Membrane Nanovesicles Enhance Brain Delivery and Therapeutic Efficacy of Irinotecan in Orthotopic Glioma

The blood-brain barrier (BBB) and hydrolytic inactivation of the lactone form limit the efficacy of irinotecan (CPT-11) against glioma. To address these challenges, we developed a CPT-11-loaded hybrid liposome-U87MG cell membrane nanovesicle formulation (Hybrid/CPT-11), an underexplored biomimetic strategy for glioma therapy. This formulation combines the drug-loading and stabilizing capacity of liposomes (Lip) with the membrane-derived functionality of biomimetic nanovesicles (BNVs) prepared from U87MG cell membranes.

Three preparation strategies-co-incubation, freeze-thaw followed by co-extrusion, and film hydration followed by co-extrusion-were compared. Membrane fusion was assessed by Förster resonance energy transfer (FRET) to select the optimal process. Physicochemical properties (TEM, hydrodynamic size/PDI, encapsulation efficiency, short-term storage and serum stability) were characterized. In vitro performance (U87MG uptake, 3D spheroid penetration, proliferation and migration inhibition) and in vivo biodistribution (Cy5 imaging), antitumor efficacy (bioluminescence imaging, tumor burden, survival), and biosafety (body weight, hematology, major-organ histology) were evaluated in orthotopic U87MG and U87MG-Luc glioma models.

Freeze-thaw followed by co-extrusion yielded the greatest FRET decrease and was selected. Hybrid/CPT-11 exhibited a uniform nanoscale size (178.4 ± 4.6 nm, PDI 0.22 ± 0.01), high encapsulation efficiency (61.6%), and stability. In vitro, Hybrid/Cou-6 showed enhanced cellular uptake and deeper penetration in 3D spheroids versus free Cou-6 and BNV/Cou-6. Hybrid/CPT-11 also exhibited the lowest IC 50 in U87MG cells compared with free CPT-11 and nonhybrid controls. In vivo, Hybrid/Cy5 prolonged systemic signal and enhanced brain accumulation versus Lip/Cy5 and BNV/Cy5. In orthotopic U87MG-Luc glioma, Hybrid/CPT-11 suppressed tumor bioluminescence, reduced endpoint tumor burden, and extended median survival (21 vs 16 days for free CPT-11), without significant weight loss, hematologic abnormalities, or major-organ pathology.

This study developed a FRET-optimized hybrid liposome-U87MG cell membrane nanovesicle formulation that enhances brain delivery and therapeutic efficacy of irinotecan in orthotopic glioma.

Abstract from PubMed Central (PMID 42999601, PMC13744199). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.