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Title: Doxorubicin conjugated, crosslinked, PEGylated particles prepared via one-pot thiol-ene modification of a homopolymer scaffold: synthesis and in vitro evaluation
Authors: Wong, Lingjiun
Kavallaris, Maria
Bulmuş, Volga
Issue Date: 2011
Publisher: Royal Society of Chemistry
Abstract: Doxorubicin (Dox)-conjugated, poly(ethylene glycol) (PEG) shielded, reversibly crosslinked particles were prepared by a one-pot thiol-ene reaction from a RAFT-synthesized well-defined homopolymer scaffold, poly(pyridyldisulfide ethylmethacrylate) (PPDSM). Dox and PEG modified with maleimide end-groups (mal-Dox and mal-PEG), were covalently attached in one pot to free thiol groups of PPDSM (M-n = 8900 g mol(-1) and PDI = 1.18) in the presence of a disulfide reducing agent. similar to 50% of the total pyridyldisulfide units were conjugated with Dox and PEG (with an equal mol ratio). Particles with an average hydrodynamic diameter of 192 +/- 28 nm were observed to form after conjugation. Incubation of these particles with a disulfide reducing agent resulted in the disassociation of the particles. The release of Dox from the particles was pH dependent. The Dox-conjugated PEGylated particles (with a Dox content of 8 wt%) inhibited the viability of human cervical carcinoma cells (HeLa) with an IC50 value of 8 X 10(-7) M, determined by an Alamar Blue assay, while the IC50 of free Dox was 1 X 10(-7) M. The fluorescence microscopy analyses of the HeLa cells after incubation with the particles for varying times showed that the Dox carried by the particles is taken up efficiently by the cells.
ISSN: 1759-9954
Appears in Collections:WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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