{'fraction_non_alphanumeric': 0.013493253373313344, 'fraction_numerical': 0.0, 'mean_word_length': 5.8561643835616435, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 1, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Differential uptake of nanoparticles by endothelial cells through polyelectrolytes with affinity for caveolae

Significance Nanoparticles (NPs) can serve as containers for the targeting of therapeutics to tumors. Tumors comprise many cell types including endothelial cells that form the blood vessels. Developing new strategies to target information preferentially to endothelial cells can have major implications in the development of targeted therapeutics. We have discovered that charged polymers containing aromatic sulfonate have pronounced affinity for caveolae, which are highly expressed by endothelial cells. By engineering the surface of lipid NPs to bear sulfonate-containing polymers, lipid NPs that are preferentially taken up by endothelial cells have been demonstrated. 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.