Reduction-sensitive hyaluronic acid nanoparticles for targeted intracellular deliery of doxorubicin

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Disulfide-containing HA dodecyl conjugates (HA-SS-DDTs) were synthesized using the facile thiol-exchange reaction as the carrier for intracellular delivery of doxorubicin (DOX). Owing to its amphiphilicity, HA-SS-DDT could form self-assembled nanoparticles in an aqueous condition. The size of the nanoparticles was in the rage of 291-333 nm. The morphology of the nanoparticles was spherical in shape. DOX was successfully encapsulated into HA-SS-DDT6 nanoparticles with high drug loading efficiency (> 90%) by the oil-in-water emulsion method. In the presence of 10 mM GSH mimicking the intracellular condition, the DOX-loaded HA-SS-DDT (HA-SS-DDT6-DOX) nanoparticles released rapidly DOX, whereas its release rate decreased remarkably in the absence of GSH. The reduction-insensitive tetradecylamine conjugated HA (HA-TDA6) nanoparticles released DOX in a sustained manner and its release rate was not dependent on the GSH concentration. The in vitro cytotoxicity assay demonstrated dose-dependent cytotoxicity for HA-SS-DDT6-DOX nanoparticles against SCC7 cancer cells, whereas the bare nanoparticles had no significant cytotoxicity even at high concentrations. Cellular imaging studies revealed higher uptake of HA-SS-DDT6-DOX than free DOX for SCC7 cancer cells that over-express HA receptors, indicating receptor-mediated endocytosis of the nanoparticles. Overall, these results suggest that HA-SS-DDT nanoparticles have promising potential as the carrier of DOX for cancer therapy.

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Journal: TechConnect Briefs
Volume: 3, Nanotechnology 2013: Bio Sensors, Instruments, Medical, Environment and Energy (Volume 3)
Published: May 12, 2013
Pages: 289 - 292
Industry sectors: Advanced Materials & Manufacturing | Medical & Biotech
Topics: Biomaterials, Materials for Drug & Gene Delivery
ISBN: 978-1-4822-0586-2