RT Journal Article
T1 Shape effect in active targeting of nanoparticles to inflamed cerebral endothelium under static and flow conditions
A1 Silva Candal, Andrés da
A1 Brown, Tyler D.
A1 Krishnan, Vinu
A1 López Loureiro, José Ignacio
A1 Ávila Gómez, Paulo
A1 Pusuluri, Anusha
A1 Pérez Díaz, Amparo
A1 Correa Paz, Clara
A1 Hervella Lorenzo, Pablo
A1 Castillo Sánchez, José Antonio
A1 Mitragotri, Samir
A1 Campos Pérez, Francisco
K1 Active targeting
K1 Brain
K1 Inflammation
K1 Shape
AB Endothelial cells represent the first biological barrier for compounds, including nanoparticles, administered via the intravascular route. In the case of ischemic stroke and other vascular diseases, the endothelium overexpresses specific markers, which can be used as molecular targets to facilitate drug delivery and imaging. However, targeting these markers can be quite challenging due to the presence of blood flow and the associated hydrodynamic forces, reducing the likelihood of adhesion to the vessel wall. To overcome these challenges, various parameters including size, shape, charge or ligand coating have been explored to increase the targeting efficiency. Geometric shape can modulate nanoparticle binding to the cell, especially by counteracting part of the hydrodynamic forces of the bloodstream encountered by the classical spherical shape. In this study, the binding affinity of polystyrene nanoparticles with two different shapes, spherical and rod-shaped, were compared. First, vascular adhesion molecule-1 (VCAM-1) was evaluated as a vascular target of inflammation, induced by lipopolysaccharide (LPS) stimulation. To evaluate the effect of nanoparticle shape on particle adhesion, nanoparticles were coated with anti-VCAM-1 and tested under static conditions in cell culture dishes coated with cerebral microvasculature cells (bEnd.3) and under dynamic flow conditions in microfluidic channels lined with hCMEC/D3 cells. Effect of particle shape on accumulation was also assessed in two in vivo models including systemic inflammation and local brain inflammation. The elongated rod-shaped particles demonstrated greater binding ability in vitro, reaching a 2.5-fold increase in the accumulation for static cultures and 1.5-fold for flow conditions. Anti-VCAM-1 coated rods exhibited a 3.5-fold increase in the brain accumulation compared to control rods. These results suggest shape offers a useful parameter in future design of drug delivery nanosystems or contrast agents for neurovascular pathologies.
PB Elsevier
SN 0168-3659
YR 2019
FD 2019
LK http://hdl.handle.net/10347/21412
UL http://hdl.handle.net/10347/21412
LA eng
NO Da Silva-Candal, A., Brown, T., Krishnan, V., Lopez-Loureiro, I., Ávila-Gómez, P., Pusuluri, A., Pérez-Díaz, A., Correa-Paz, C., Hervella, P., Castillo, J., Mitragotri, S., & Campos, F. (2019). Shape effect in active targeting of nanoparticles to inflamed cerebral endothelium under static and flow conditions. Journal of Controlled Release, 309, 94-105. https://doi.org/10.1016/j.jconrel.2019.07.026
NO This study has been partially supported by grants from Instituto de Salud Carlos III (PI13/00292 and PI17/0054), Spanish ResearchNetwork on Cerebrovascular Diseases RETICS-INVICTUS (RD12/0014),Fundación  Mutua  Madrileña.  The  Ministry  of  Economy  and Competitiveness of Spain (SAF2017-84267-R). The European Union program FEDER and the European Regional Development Fund–ERDF, MADIA project No. 732678 to FC. Furthermore, F. Campos (CP14/00154) recipients a research contract from Miguel Servet Program of Instituto de Salud Carlos III. National Science Foundation Graduate Research Fellowship under Grant DGE-1745303
DS Minerva
RD 24 abr 2026