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Minimizing antibody surface density on liposomes while sustaining cytokine-activated EC targeting
Dariela Almeda1, Biran Wang2, Debra T Auguste2
1School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Biomaterials
|December 20, 2014
Summary
Engineered liposomes target inflamed endothelium by mimicking cell adhesion molecules like VCAM1 and E-selectin. This novel design enhances drug delivery to inflamed sites with reduced antibody usage.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cell Biology
Background:
- Inflamed endothelium, characterized by VCAM1 and E-selectin upregulation, presents a target for drug delivery in diseases like atherosclerosis and cancer.
- Leukocyte-endothelial cell interactions offer a model for designing targeted liposomes that mimic natural ligand-receptor binding.
Purpose of the Study:
- To engineer liposomes that specifically target inflamed endothelium by optimizing antibody targeting strategies.
- To quantify the optimal antibody density, ratio, and liposome diffusivity for effective binding and internalization by endothelial cells.
Main Methods:
- Characterized endothelial cell (EC) surfaces by measuring E-selectin and VCAM1 densities and adhesion forces.
- Quantified antibody density, ratio, and liposome diffusivity to determine optimal parameters for liposome binding and uptake.
- Compared binding and uptake efficiency of liposomes functionalized with varying ratios of anti-VCAM1 and anti-E-selectin antibodies.
Main Results:
- A 1:1 ratio of VCAM1:E-selectin antibodies showed significantly higher binding and internalization than other ratios.
- Effective binding and uptake were achieved at lower anti-E-selectin densities (400 molecules/μm²) than previously reported.
- Optimal targeting was achieved with a 1:1 antibody ratio at 1000 molecules/μm², an 85% reduction in density compared to prior studies.
- Reduced liposome membrane diffusivity significantly decreased targeted binding and uptake.
Conclusions:
- Developed a liposomal design that effectively targets inflamed endothelium by mimicking leukocyte-endothelial interactions.
- Achieved significant binding and internalization with optimized antibody density and ratio, reducing the required antibody amount.
- The study provides a strategy for discriminating between healthy and inflamed endothelium, paving the way for improved targeted drug delivery systems.
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