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Biodegradable nanogels prepared by atom transfer radical polymerization as potential drug delivery carriers: synthesis, biodegradation, in vitro release, and bioconjugation
Authors:Oh Jung Kwon  Siegwart Daniel J  Lee Hyung-il  Sherwood Gizelle  Peteanu Linda  Hollinger Jeffrey O  Kataoka Kazunori  Matyjaszewski Krzysztof
Institution:Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA.
Abstract:Stable biodegradable nanogels cross-linked with disulfide linkages were prepared by inverse miniemulsion atom transfer radical polymerization (ATRP). These nanogels could be used for targeted drug delivery scaffolds for biomedical applications. The nanogels had a uniformly cross-linked network, which can improve control over the release of encapsulated agents, and the nanogels biodegraded into water-soluble polymers in the presence of a biocompatible glutathione tripeptide, which is commonly found in cells. The biodegradation of nanogels can trigger the release of encapsulated molecules including rhodamine 6G, a fluorescent dye, and Doxorubicin (Dox), an anticancer drug, as well as facilitate the removal of empty vehicles. Results obtained from optical fluorescence microscope images and live/dead cytotoxicity assays of HeLa cancer cells suggested that the released Dox molecules penetrated cell membranes and therefore could suppress the growth of cancer cells. Further, OH-functionalized nanogels were prepared to demonstrate facile applicability toward bioconjugation with biotin. The number of biotin molecules in each nanogel was determined to be 142,000, and the formation of bioconjugates of nanogels with avidin was confirmed using optical fluorescence microscopy.
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