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


BACKGROUND
In this basic science study, a highly efficient targeted doxorubicin delivery method to hepatocytes is presented.
Lu
Changhai
C
Department of Textile Sciences, Faculty of Human Ecology, University of Manitoba, Winnipeg, Manitoba, Canada.
Xing
Malcolm M Q
MM
Zhong
Wen
W
D004317:Doxorubicin / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007785:Lactose / Q000737:chemistry; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry
D004337:Drug Carriers; D011092:Polyethylene Glycols; D004317:Doxorubicin; D007785:Lactose