The fabrication and evaluation of a natural pectin-based drug delivery system are reported in this study. The drug delivery system displays specific active targeting ability to hepatocellular carcinoma due to the presence of excess galactose residues in the polymer structure as the natural targeting ligands. The system was prepared under very mild conditions in an aqueous medium containing Ca(2+) and CO3(2-) ions, generating uniform pectin-based nanoparticles with an average diameter of 300 nm, and the drug-loading content of anticancer drug 5-fluorouracil (5-FU) is around 24.8%. Cytotoxicity study of the 5-FU-loaded nanoparticles (5-FU-NPs) in HepG2 and A549 cell lines demonstrated their greater potency in killing cancer cells with overexpressed asialoglycoprotein receptor (ASGPR) on the cell surface, compared to that of the free drug. Pharmacokinetics study using Sprague-Dawley (SD) rats further confirmed that the drug-loaded nanoparticles showed a much longer half-life in the circulation fluids than the free drug. Tissue distribution was investigated on Kunming mice, and the results also demonstrated that the 5-FU-NPs has a long circulation effect. Taken together, the pectin-based drug delivery systems exhibit size-induced prolonged circulation as well as ASGP receptor-mediated targeting ability to cancer cell lines; therefore, it is a promising platform for the treatment of hepatocellular carcinoma.
A novel type of macromolecular prodrug delivery system is reported in this research. The N-galactosylated-chitosan-5-fluorouracil acetic acid conjugate (GC-FUA) based nanoparticle delivery system was evaluated in vitro and in vivo. Biocompatibility of GC-FUA-NPs was screened by BSA adsorption test and hemolysis activity examination in vitro. Cytotoxicity and cellular uptake study in HepG2 and A549 cells demonstrated that compared to free 5-Fu, the GC-FUA-NPs play great function in killing cancer cells for the cell endocytosis mediated by asialoglycoprotein receptor (ASGPR), which overexpresses on the cell surface. Pharmacokinetics study further illustrated that the drug-loaded nanoparticles has a much longer half-time than free 5-Fu in blood circulation in Sprague-Dawley (SD) rats. Tissue distribution was investigated in Kunming mice, and the result showed that the GC-FUA-NPs have a long circulation effect. The obtained data suggested that GC-FUA-NP is a very promising drug delivery system for efficient treatment of hepatocellular carcinoma.
In this study, a novel type of macromolecular prodrug, N-galactosylated chitosan (GC)25-fluorouracil acetic acid (FUA) conjugate based nanoparticles, was designed and synthesized as a carrier for hepatocellular carcinoma drug delivery. The GC-FUA nanoparticles were produced by an ionic crosslinking method based on the modified ionic gelation of tripolyphosphate with GC-FUA. The structure of the as-prepared GC-FUA was characterized by Fourier transform infrared and 1 H-NMR analyses. The average particle size of the GC-FUA nanoparticles was 160.1 nm, and their drug-loading content was 21.22 6 2.7% (n 5 3). In comparison with that of the freshly prepared nanoparticles, this value became larger after 7 days because of the aggregation of the GC-FUA nanoparticles. An in vitro drug-release study showed that the GC-FUA nanoparticles displayed a sustained-release profile compared to 5-fluorouracil-loaded GC nanoparticles. All of the results suggest that the GC-FUA nanoparticles may have great potential for antiliver-cancer applications.
Well-defined gold embedded maghemite hybrid nanowires are synthesized, and their structures are fully characterized. They are composed of porous γ-Fe2O3 shells and embedded gold nanoparticles (3-10 nm), which is novel and very different from the conventional "surface decoration" configuration. These hybrid nanowires are produced by the de-alloying of Au-Fe alloy nanowires and subsequent heat treatment. The reaction mechanism is proposed and validated. The results of X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and thermogravimetry techniques prove consistently that the Fe composition of Au-Fe alloy nanowires change to γ-FeOOH first and then to γ-Fe2O3. The embedded gold particles are help to enhance the gas response properties of the hybrid nanowires, which is attributed to the nano open-circuit Schottky junctions between γ-Fe2O3 and the Au nanoparticles. The gas sensing experiment data with high repeatability demonstrate that these hybrid nanowires are excellent sensing materials, especially for ethanol, and have shown both high selectivity and high sensitivity.
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