Related Experiment Video
Updated: Jun 11, 2025
Author Spotlight: Innovative Cancer Therapies with Iron Oxide Nanoparticles for Glioblastoma Treatment
Published on: September 27, 2024
Increased Cellular Uptake of ApoE3- or c(RGD)-Modified Liposomes for Glioblastoma Therapy Depending on the Target
Larissa J Lubitz1,2,3, Moritz P Haffner1, Harden Rieger1,2
1ABNOBA GmbH, 75223 Niefern-Öschelbronn, Germany.
Abstract:
As effective treatment of glioblastoma is still an unmet need, targeted delivery systems for efficient treatment are of utmost interest. Therefore, in this paper, surface modifications with a small peptide c(RGD) or physiological protein (ApoE3) were investigated. Cellular uptake in murine endothelial cells (bEnd.3) and different glioma cells (human U-87 MG, rat F98) was tested to elucidate possible differences and to correlate the uptake to the receptor expression. Different liposomal formulations were measured at 1 and 3 h for three lipid incubation concentrations. We calculated the liposomal uptake saturation S and the saturation half-time t1/2. An up to 9.6-fold increased uptake for ApoE3-modified liposomes, primarily in tumor cells, was found. Contrarily, c(RGD) liposomes showed a stronger increase in uptake in endothelial cells (up to 40.5-fold). The uptake of modified liposomes revealed enormous differences in S and t1/2 when comparing different tumor cell lines. However, for ApoE3-modified liposomes, we proved comparable saturation values (~25,000) for F98 cells and U-87 MG cells despite a 6-fold lower expression of LRP1 in F98 cells and a 5-fold slower uptake rate. Our findings suggest that cellular uptake of surface-modified liposomes depends more on the target structure than the ligand type, with significant differences between cell types of different origins.
Insights
Surface modifications of liposomes with ApoE3 or c(RGD) peptides enhance cellular uptake for glioblastoma treatment. ApoE3 liposomes show increased tumor cell uptake, while c(RGD) liposomes target endothelial cells effectively.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Glioblastoma treatment remains a significant clinical challenge, necessitating advanced drug delivery systems.
- Targeted liposomal delivery systems offer potential for enhanced glioblastoma therapy.
- Surface modification of liposomes can improve cellular targeting and drug efficacy.
Purpose of the Study:
- To investigate the effect of surface modifications on liposome cellular uptake in glioblastoma models.
- To compare the targeting efficiency of ApoE3 and c(RGD) modified liposomes in different cell types.
- To correlate liposome uptake with receptor expression levels in endothelial and glioma cells.
Main Methods:
- Liposomes were surface-modified with the peptide c(RGD) or the protein ApoE3.
- Cellular uptake studies were conducted using murine endothelial cells (bEnd.3) and glioma cells (U-87 MG, F98).
- Liposomal uptake saturation (S) and saturation half-time (t1/2) were quantified at various incubation times and concentrations.
Main Results:
- ApoE3-modified liposomes demonstrated up to a 9.6-fold increase in uptake, primarily in tumor cells.
- c(RGD)-modified liposomes showed a significant increase in uptake in endothelial cells (up to 40.5-fold).
- Comparable saturation values for ApoE3 liposomes in F98 and U-87 MG cells were observed, despite differences in LRP1 expression and uptake rates.
Conclusions:
- Cellular uptake of surface-modified liposomes is significantly influenced by the target cell's structure rather than solely the ligand type.
- ApoE3 and c(RGD) modifications offer distinct targeting capabilities for endothelial and tumor cells, respectively.
- These findings provide valuable insights for designing targeted liposomal drug delivery systems for glioblastoma.
