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• W2015202374 abstract "Long-circulating nanocarriers have been extensively studied to deliver chemotherapeutics; however, the inclusion of targeting agents compromises circulation times thereby offsetting the benefits of active targeting. Here, we formulated cysteine-cleavable phospholipid-polyethylene glycol (PEG) to 'mask' nanocarrier bound targeting ligands from RES clearance and prolong circulation times of liposomes to allow passive targeting to tumors. This detachable polymer coating can be removed after nanocarrier extravasation to tumor is achieved to expose targeting ligands and promote active targeting to tumor cells. In vivo studies on folate receptor-targeted liposomes demonstrated our ability to prolong circulation in the bloodstream using this system thereby verifying the 'masking' capacity of cleavable phospholipid-PEG(5000). Controlled modulation of uptake and cytotoxicity of targeted nanocarriers using cleavable phospholipid-PEG was demonstrated through in vitro studies. Finally, studies analyzing uptake by tumor cells in vivo confirmed enhanced intracellular delivery when tumor-inoculated animals received targeted liposomes containing cleavable phospholipid-PEG(5000) followed by a cysteine infusion to expose folate after liposomes had extravasated to tumor. These results indicate that cleavable phospholipid-PEG can be used in nanocarrier formulations for controlled exposure of targeting ligands to ensure that circulation times remain uncompromised by the inclusion of targeting agents while enabling active targeting to tumors after removal of the polymer coating." @default.
• W2015202374 created "2016-06-24" @default.
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• W2015202374 creator A5046943484 @default.
• W2015202374 creator A5056398760 @default.
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• W2015202374 date "2009-08-01" @default.
• W2015202374 modified "2023-10-16" @default.
• W2015202374 title "Masking and triggered unmasking of targeting ligands on nanocarriers to improve drug delivery to brain tumors" @default.
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• W2015202374 doi "https://doi.org/10.1016/j.biomaterials.2009.04.012" @default.
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