Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 8, Pages 2942-2947Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1322356111
Keywords
polyanion; aromatic polysulfonates; polystyrene sulfonate; vasculature
Categories
Funding
- 5th INTERREG Upper Rhine Program [A21: NANO@MATRIX]
- excellence initiative of the German Federal Government (Centre for Biological Signalling Studies, BIOSS) [EXC 294]
- excellence initiative of the German State Government (Centre for Biological Signalling Studies, BIOSS) [EXC 294]
- University of Freiburg
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Nanoparticles (NPs) constitute an important medium for the targeted delivery of cancer therapeutics. Targeting of NPs to a specific cell type is traditionally achieved through the modification of the NP surface with peptides, aptamers, or other motifs that specifically recognize a cell-surface receptor, leading to internalization of NPs via clathrin and caveolae-mediated endocytosis. We have discovered that modifying the NP surface with anionic polyelectrolytes of varying lipophilicity can regulate the uptake of lipid NPs by endothelial and epithelial cells. Furthermore, we report the finding that synthetic polyelectrolytes composed of an aromatic sulfonic acid backbone exhibit specific affinity for caveolae of endothelial cells. By exploiting the higher expression of caveolae in endothelial cells in comparison with epithelial cells, a purely physiochemical approach to the targeted uptake of lipid NPs to endothelial cells is demonstrated. The ability to confer preferential affinity for NPs to cell surface domains by varying the charge and lipophilic characteristics of an NP surface offers a general means of achieving targeted delivery without the need for receptor-ligand-type targeting strategies.
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