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Published on: October 19, 2015
Targeting microparticles to select tissue via radiation-induced upregulation of endothelial cell adhesion molecules
Mohammad F Kiani1, Hong Yuan, Xin Chen
1School of Biomedical Engineering, Department of Radiation Oncology, University of Tennessee Health Science Center, Memphis 38163, USA. mkiani@utmem.edu
Purpose:
Certain endothelial cell adhesion molecules are up regulated in tissue that has been irradiated for therapeutic purposes. This up-regulation of adhesion molecules provides a potential avenue for targeting drugs to select tissues.
Methods:
Microspheres were coated with a mAb to ICAM-1 and the level of adhesion of the anti-ICAM-1 microspheres to irradiated tissue in vitro and in vivo was quantified.
Results:
Under in vitro flow conditions, the number of adherent microspheres on irradiated HUVEC was 4.8 +/- 0.9 times that of control; the adhesion of anti-ICAM-1 microspheres on irradiated HUVEC could be enhanced by more than 170% in the presence of RBC (20% hematocrit) in the medium. In vivo in a rat cranial window model, the number of adherent anti-ICAM-1 microspheres in locally irradiated cerebral tissue was 8 and 13 times that of IgG microspheres at 24 h and 48 h post-irradiation, respectively and returned to baseline 7 days post-irradiation. In locally irradiated animals, the number of adhering microspheres in unirradiated tissue remained at the basal level.
Conclusions:
Radiation-induced up-regulation of endothelial cell adhesion molecules may be exploited to target drugs and/or genes to select segments of the endothelium.
Insights
Targeted drug delivery is enhanced by exploiting radiation-induced up-regulation of endothelial cell adhesion molecules. Anti-ICAM-1 microspheres effectively target irradiated tissue, showing increased adhesion in vitro and in vivo.
Area of Science:
- Biomedical Engineering
- Oncology
- Vascular Biology
Background:
- Therapeutic radiation up-regulates endothelial cell adhesion molecules.
- This up-regulation presents an opportunity for targeted drug delivery to specific tissues.
Purpose of the Study:
- To investigate the potential of targeting drugs to irradiated tissues.
- To quantify the adhesion of anti-ICAM-1 microspheres to irradiated tissue.
Main Methods:
- Microspheres were coated with a monoclonal antibody (mAb) to ICAM-1.
- Adhesion of anti-ICAM-1 microspheres to irradiated tissue was assessed in vitro and in vivo using a rat cranial window model.
Main Results:
- In vitro, adherent microspheres on irradiated endothelial cells increased 4.8-fold compared to controls.
- In vivo, anti-ICAM-1 microspheres showed 8-13 times greater adhesion in irradiated cerebral tissue compared to IgG microspheres.
- Adhesion returned to baseline levels within 7 days post-irradiation, with no significant adhesion in unirradiated tissue.
Conclusions:
- Radiation-induced up-regulation of endothelial cell adhesion molecules can be leveraged for targeted delivery.
- This approach holds promise for delivering drugs and/or genes to specific endothelial segments.
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