Targeting efficiency of nanoliposomes on atherosclerotic foam cells: polyethylene glycol-to-ligand ratio effects

ABSTRACT

Background

Nanoparticles that actively target tissues, with ligands attached at the extremity of polyethylene glycol (PEG) spacer, are a promising strategy to enhance target cell specificity and internalization. However, the interplay between the targeting ligands and the adjacent ligand-free PEG remains poorly understood.

Research design and methods

Experimentally, liposomes containing active folate ligands were firstly formulated and the optimum amount of ligand that yields the highest foam cell uptake was determined. Subsequently, ligand-free PEG was incorporated, and the effects of PEG lengths and concentrations on foam cell uptake were evaluated after the nanoparticles were incubated in human serum for 90 min.

Results

It was demonstrated that the targeting efficiency progressively decreased and was eventually annulled as PEG-to-ligand ratio was increased, with loss of targeting effect occurring at PEG-to-ligand ratio of >2 for PEG 750, >0.5 for PEG 2000 and <0.5 for PEG 5000.

Conclusions

This work demonstrates that PEG-to-ligand ratio and serum coating on nanoparticle surface are both important features to be considered in the design of active targeting nanocarriers. This work also supports the development of novel active targeting nanotherapies for atherosclerosis.

KEYWORDS:

• Polyethylene glycol
• liposome
• atherosclerosis
• foam cells

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was supported by NTU – Northwestern Institute for Nanomedicine (project: nanotechnology to diagnose, prevent, and treat cardiovascular disease).