Shell cross-linked and hepatocyte-targeting nanoparticles containing doxorubicin via acid-cleavable linkage

Nanomedicine : Nanotechnology, Biology, and Medicine
Changhai LuWen Zhong

Abstract

Hepatocyte-targeting and shell cross-linked nanoparticles with lactose moiety on the surface and doxorubicin (DOX) in the core were prepared from lactose-PEG-DOX conjugate. The process consists of the synthesis of a novel α-hydrazine-ω-propargyl poly(ethylene glycol) (PEG) with a double bond in the PEG backbone, followed by the bonding of a lactose molecule containing an azide group to the ω-end of PEG via "click" chemistry, and finally, the conjugation of DOX to the α-end of PEG via an acid-labile, hydrazone linkage. The resultant conjugate can be self-assembled into nanoparticles. Thiolated tri(ethylene glycol) was introduced into the shell of nanoparticles as a cross-linking agent. The release of DOX is more rapid from lactose-PEG-DOX at pH 5.0 than at pH 7.4. Fluorescent microscope studies suggest that the lactose-DOX nanoparticles are internalized by hepatoma cells through a lactose receptor-mediated mechanism, whereas the lactose-free nanoparticles are not endocytosed as rapidly as lactose-DOX nanoparticles. MTT assay also shows that lactose-DOX nanoparticles have a stronger inhibition against hepatoma cells than DOX nanoparticles and pure DOX. In this basic science study, a highly efficient targeted doxorubicin delivery ...Continue Reading

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Citations

Sep 26, 2013·Advanced Drug Delivery Reviews·Yuanpei LiKit S Lam
Feb 20, 2014·Drug Delivery·Bita TaghizadehZaynab Derakhshani
Apr 25, 2013·Journal of Biomedical Materials Research. Part a·Huanan LiXingdong Zhang
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Mar 28, 2013·ACS Applied Materials & Interfaces·Jun ChenMalcolm Mq Xing

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