Abstract
Surgical resection remains the primary treatment modality for glioblastoma (GBM); however, the infiltrative nature of GBM margins complicates achieving complete tumor removal. Additionally, the blood-brain barrier (BBB) poses a formidable challenge to effective probe delivery, thereby hindering precise imaging-guided surgery. Here, we introduce hybrid cell membrane-coated indocyanine green (ICG) liposomes (HM-Lipo-ICG) as biomimetic near-infrared (NIR) fluorescent probes for targeted BBB penetration and accurate delineation of infiltrative GBM margins. HM-Lipo-ICG encapsulates clinically approved ICG within its core and utilizes a hybrid cell membrane exterior, enabling specific targeting and enhanced BBB permeation. Quantitative assessments demonstrate that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes. Mechanistically, CD44 receptor-mediated endocytosis facilitates BBB translocation of HM-Lipo-ICG. Furthermore, HM-Lipo-ICG enables high-contrast NIR imaging, achieving a signal-to-background ratio of 6.5 in GBM regions of an orthotopic glioma mouse model, thereby improving tumor margin detection accuracy fourfold (84.4% vs. 22.7%) compared to conventional ICG liposomes. Application of HM-Lipo-ICG facilitates fluorescence-guided precision surgery, resulting in complete resection of GBM cells. This study underscores the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins.
Overview
- The study aims to develop a biomimetic near-infrared (NIR) fluorescent probe for targeted blood-brain barrier (BBB) penetration and accurate delineation of infiltrative glioblastoma (GBM) margins. The study introduces hybrid cell membrane-coated indocyanine green (ICG) liposomes (HM-Lipo-ICG) as a potential solution to the challenges posed by the infiltrative nature of GBM margins and the BBB. The study's primary objective is to demonstrate the effectiveness of HM-Lipo-ICG in achieving BBB penetration and improving tumor margin detection accuracy in an orthotopic glioma mouse model. The study utilizes a hybrid cell membrane exterior and CD44 receptor-mediated endocytosis to facilitate BBB translocation and enhance the probe's fluorescence signal. The study's findings suggest that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes and enables high-contrast NIR imaging, improving tumor margin detection accuracy fourfold compared to conventional ICG liposomes. The study's findings underscore the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions, specifically the use of HM-Lipo-ICG versus conventional ICG liposomes. The study found that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes. Additionally, HM-Lipo-ICG enables high-contrast NIR imaging, achieving a signal-to-background ratio of 6.5 in GBM regions of an orthotopic glioma mouse model, thereby improving tumor margin detection accuracy fourfold (84.4% vs. 22.7%) compared to conventional ICG liposomes. The study's findings suggest that HM-Lipo-ICG is a more effective solution for targeted BBB penetration and accurate delineation of infiltrative GBM margins compared to conventional ICG liposomes.
Implications and Future Directions
- The study's findings have significant implications for the field of research and clinical practice. The study demonstrates the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins. The study's findings suggest that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes and enables high-contrast NIR imaging, improving tumor margin detection accuracy fourfold compared to conventional ICG liposomes. The study's findings underscore the potential of hybrid cell membrane-coated liposomal probes in improving the accuracy and effectiveness of surgical resection for GBM. Future research directions could explore the use of HM-Lipo-ICG in clinical settings and investigate the potential of HM-Lipo-ICG in combination with other imaging modalities to further enhance the accuracy of GBM margin delineation.