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Vascular targeting of nanocarriers: perplexing aspects of the seemingly straightforward paradigm.
- Source :
-
ACS nano [ACS Nano] 2014 May 27; Vol. 8 (5), pp. 4100-32. Date of Electronic Publication: 2014 May 07. - Publication Year :
- 2014
-
Abstract
- Targeted nanomedicine holds promise to find clinical use in many medical areas. Endothelial cells that line the luminal surface of blood vessels represent a key target for treatment of inflammation, ischemia, thrombosis, stroke, and other neurological, cardiovascular, pulmonary, and oncological conditions. In other cases, the endothelium is a barrier for tissue penetration or a victim of adverse effects. Several endothelial surface markers including peptidases (e.g., ACE, APP, and APN) and adhesion molecules (e.g., ICAM-1 and PECAM) have been identified as key targets. Binding of nanocarriers to these molecules enables drug targeting and subsequent penetration into or across the endothelium, offering therapeutic effects that are unattainable by their nontargeted counterparts. We analyze diverse aspects of endothelial nanomedicine including (i) circulation and targeting of carriers with diverse geometries, (ii) multivalent interactions of carrier with endothelium, (iii) anchoring to multiple determinants, (iv) accessibility of binding sites and cellular response to their engagement, (v) role of cell phenotype and microenvironment in targeting, (vi) optimization of targeting by lowering carrier avidity, (vii) endocytosis of multivalent carriers via molecules not implicated in internalization of their ligands, and (viii) modulation of cellular uptake and trafficking by selection of specific epitopes on the target determinant, carrier geometry, and hydrodynamic factors. Refinement of these aspects and improving our understanding of vascular biology and pathology is likely to enable the clinical translation of vascular endothelial targeting of nanocarriers.
- Subjects :
- Animals
Binding Sites
Cell Adhesion Molecules physiology
Enzymes physiology
Humans
Hydrodynamics
Intercellular Adhesion Molecule-1 physiology
Ligands
Phenotype
Platelet Endothelial Cell Adhesion Molecule-1 physiology
Protein Binding
Drug Delivery Systems
Endothelium, Vascular drug effects
Nanomedicine methods
Nanoparticles chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1936-086X
- Volume :
- 8
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- ACS nano
- Publication Type :
- Academic Journal
- Accession number :
- 24787360
- Full Text :
- https://doi.org/10.1021/nn500136z