A galactosamine-mediated drug delivery carrier for targeted liver cancer therapy

School of Chemical Engineering, The University of Adelaide, Adelaide SA5005, Australia.
Pharmacological Research (Impact Factor: 4.41). 06/2011; 64(4):410-9. DOI: 10.1016/j.phrs.2011.06.015
Source: PubMed


In order to minimize the side effect of cancer chemotherapy, a novel galactosamine-mediated drug delivery carrier, galactosamine-conjugated albumin nanoparticles (GAL-AN), was developed for targeted liver cancer therapy. The albumin nanoparticles (AN) and doxorubicin-loaded AN (DOX-AN) were prepared by the desolvation of albumin in the presence of glutaraldehyde crosslinker. Morphological study indicated the spherical structure of these synthesized particles with an average diameter of around 200 nm. The functional ligand of galactosamine (GAL) was introduced onto the surfaces of AN and DOX-AN via carbodiimide chemistry to obtain GAL-AN and GAL-DOX-AN. Cellular uptake and kinetic studies showed that GAL-AN is able to be selectively incorporated into the HepG2 cells rather than AoSMC cells due to the existence of asialoglycoprotein receptors on HepG2 cell surface. The cytotoxicity, measured by MTT test, indicated that AN and GAL-AN are non-toxic and GAL-DOX-AN is more effective in HepG2 cell killing than that of DOX-AN. As such, our results implied that GAL-AN and GAL-DOX-AN have specific interaction with HepG2 cells via the recognition of GAL and asialoglycoprotein receptor, which renders GAL-AN a promising anticancer drug delivery carrier for liver cancer therapy.

Download full-text


Available from: Zheyu Shen, Apr 02, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications.
    Preview · Article · Jan 2012 · Theranostics
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Five pH-responsive alkyne-poly(2-aminoethyl methacrylate)-graft-poly(L-glutamic acid) (alkyne-PAMA-g-PLGA) comb copolymers were synthesized through the ring-opening polymerization (ROP) of γ-benzyl-L-glutamate N-carboxyanhydride (BLG NCA) and the subsequent deprotection of benzyl group from BLG unit. The chemical structures of copolymers were confirmed by proton nuclear magnetic resonance spectra (1H NMR) and Fourier transform infrared spectroscopy (FTIR). The pyrene-probe-based fluorescence technique and transmission electron microscopy (TEM) measurements revealed that the comb copolymers could spontaneously self-assemble into micellar or vesicular nanoparticles in phosphate buffered saline (PBS) at pH 7.4. Doxorubicin (DOX), an anthracycline anticancer drug, was loaded into nanoparticles as a model anticancer drug. The in vitro release results showed that the release behaviors could be altered by adjusting the composition of the comb copolymer and pH of the release medium. In vitro methyl thiazolyl tetrazolium (MTT) assays demonstrated that the copolymers were biocompatible, and DOX-loaded nanoparticles showed effective inhibition of cellular proliferation. Hemolysis tests indicated that the copolymers were also hemocompatible, and that the presence of the copolymers could reduce the hemolysis ratio (HR) of the DOX significantly. In addition, the comb copolymers could be modified through versatile Cu(I)-catalyzed “click chemistry” between the terminal alkyne group and azide-modified functional agents. These properties indicate that the pH-responsive clickable comb copolymers are promising candidates for multifunctional nanocarriers in cancer diagnosis and therapy.
    Full-text · Article · Mar 2012 · Macromolecular Research
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we report the application of a biocompatible thermo-reversible hydrogel, made from thermo-sensitive poly(N-isopropylacrylamide-co-acrylic acid) (P(NIPAM-AA)) microgels, for expanding stem cells in three-dimensions (3-D). The P(NIPAM-AA) microgels were synthesized by emulsion polymerization with their thermo-responsive phase transition behaviors being examined by light scattering and rheological methods. The viability of the microgel-exposed C3H/10T1/2 cells compared to the control cells is close to 100%, indicating the non-cytotoxicity of the synthesized microgels. At 37 °C, rheological measurements reveal the formation of hydrogels from 30 mg mL−1 microgel dispersions. The cross-sectional morphologies of the hydrogels show the interconnected porous structure. The 3-D stem cell culture system can be achieved by heating the microgel and cell mixtures to 37 °C. The increase of the viable stem cells cultured suggests that the in situ formed hydrogels support stem cell proliferation. The recovery of the 3-D cultured stem cells can be easily accomplished by cooling the culture system to room temperature. The released 3-D cultured cells can further adhere to a 2-D substrate, implying that the cultured stem cells are not only alive, but also retain the capability of migration. Therefore, the in situ formed thermo-reversible P(NIPAM-AA) hydrogels can be employed to expand stem cells in 3-D for further applications in tissue engineering.
    Full-text · Article · Jun 2012 · Soft Matter
Show more