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Prabaharan M, Grailer JJ, Pilla S, Steeber DA, Gong S: Gold nanoparticles with a monolayer of doxorubicin-conjugated amphiphilic block copolymer for tumor-targeted drug delivery. Biomaterials. 2009 Oct;30(30):6065-75. Epub 2009 Aug 12.
Gold (Au) nanoparticles (NPs) stabilized with a monolayer of folate-conjugated poly (L-aspartate-doxorubicin)-b-poly (ethylene glycol) copolymer (Au-P (LA-DOX)-b-PEG-OH/FA) was synthesized as a tumor-targeted drug delivery carrier. The Au-P (LA-DOX)-b-PEG-OH/FA NPs consist of an Au core, a hydrophobic poly (l-aspartate-doxorubicin) (P (LA-DOX)) inner shell, and a hydrophilic poly (ethylene glycol) and folate-conjugated poly (ethylene glycol) outer shell (PEG-OH/FA). The anticancer drug, doxorubicin (DOX), was covalently conjugated onto the hydrophobic inner shell by acid-cleavable hydrazone linkage. The DOX loading level was determined to be 17 wt%. The Au-P (LA-DOX)-b-PEG-OH/FA NPs formed stable unimolecular micelles in aqueous solution. The size of the Au-P (LA-DOX)-b-PEG-OH/FA micelles were determined as 24-52 and 10-25 nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The conjugated DOX was released from the Au-P (LA-DOX)-b-PEG-OH/FA micelles much more rapidly at pH 5.3 and 6.6 than at pH 7.4, which is a desirable characteristic for tumor-targeted drug delivery. Cellular uptake of the Au-P (LA-DOX)-b-PEG-OH/FA micelles facilitated by the folate-receptor-mediated endocytosis process was higher than that of the micelles without folate. This was consistent with the higher cytotoxicity observed with the Au-P (LA-DOX)-b-PEG-OH/FA micelles against the 4T1 mouse mammary carcinoma cell line. These results suggest that Au-P (LA-DOX)-b-PEG-OH/FA NPs could be used as a carrier with pH-triggered drug releasing properties for tumor-targeted drug delivery. |
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