Hybrid Liposome-U87MG Membrane Nanovesicles Enhance Brain Delivery and Therapeutic Efficacy of Irinotecan in Orthotopic Glioma.
- 1Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People's Republic of China.
- 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Hebei Medical University, Shijiazhuang, Hebei, 050000, People's Republic of China.
- 3Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 610064, People's Republic of China.
Abstract
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 IC50 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.
Related
- Cell Membrane-Coated Nanoparticles as Biomimetic Drug Delivery Systems: Design, Therapeutic Applications, and Translational Challenges.
- Liposome-based responsive MRI contrast agents
- Color-tunable luminescent TbxEuy(BDC) complexes assembled within liposome-based nanoreactors
- Development of an innovative method to enhance doxorubicin loading into erythrocyte-derived nanovesicles for breast cancer drug delivery
- Mechanism-driven nano-therapeutic platform integrating plant-derived compounds and membrane-active peptides reprograms inflammatory, cell cycle arrest, cGAS–STING, and apoptotic gene expression to quench colorectal cancer
BibTeX
@article{li2026hybrid,
title = {{Hybrid Liposome-U87MG Membrane Nanovesicles Enhance Brain Delivery and Therapeutic Efficacy of Irinotecan in Orthotopic Glioma.}},
author = {Sai Li and Yumeng Sun and Yixuan Liu and Qingqing An and Chenchen Liu and Hairui Cui and Zhifeng Zhang and Huile Gao and Baohai Yu and Bai Xiang and Jiankai Yang},
journal = {International journal of nanomedicine},
year = {2026},
month = nov,
doi = {10.2147/ijn.s633910},
url = {https://europepmc.org/article/MED/42999601},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Hybrid Liposome-U87MG Membrane Nanovesicles Enhance Brain Delivery and Therapeutic Efficacy of Irinotecan in Orthotopic Glioma.
AU - Sai Li
AU - Yumeng Sun
AU - Yixuan Liu
AU - Qingqing An
AU - Chenchen Liu
AU - Hairui Cui
AU - Zhifeng Zhang
AU - Huile Gao
AU - Baohai Yu
AU - Bai Xiang
AU - Jiankai Yang
PY - 2026
DA - 2026/11/03
JO - International journal of nanomedicine
DO - 10.2147/ijn.s633910
UR - https://europepmc.org/article/MED/42999601
AB - 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 IC50 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.
SN - 1176-9114
SN - 1178-2013
ER -