Hyaluronic acid-coated gold nanorods enhancing BMP-2 peptide delivery for chondrogenesis
| Autor: | Pakkanun Kaewkong, Kanokwan Sansanaphongpricha, Wasana Kosorn, Suwussa Bamrungsap, Pacharapan Sonthithai, Boonlom Thavornyutikarn, Nattika Saengkrit, Tapanee Thinbanmai |
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| Rok vydání: | 2020 |
| Předmět: |
Materials science
Swine Cell Bone Morphogenetic Protein 2 Bioengineering Peptide 02 engineering and technology 010402 general chemistry Endocytosis 01 natural sciences Epitope Cell Line Mice chemistry.chemical_compound Hyaluronic acid medicine Animals Humans General Materials Science Viability assay Hyaluronic Acid Electrical and Electronic Engineering Cytotoxicity chemistry.chemical_classification Drug Carriers Nanotubes Mechanical Engineering Mesenchymal Stem Cells General Chemistry 021001 nanoscience & nanotechnology Chondrogenesis 0104 chemical sciences medicine.anatomical_structure chemistry Mechanics of Materials Biophysics Gold Peptides 0210 nano-technology |
| Zdroj: | Nanotechnology. 31:435101 |
| ISSN: | 1361-6528 0957-4484 |
| DOI: | 10.1088/1361-6528/aba46d |
| Popis: | Bone morphogenic protein-2 (BMP-2) knuckle epitope peptide has been recently discovered and known to activate chondrogenesis. However, the applications of this soluble peptide remain very limited due to rapid diffusion resulting in poor cellular uptake into target cells. We herein designed nanoparticles made from hyaluronic acid functionalized gold nanorods (GNRs) to conjugate with thiolated BMP-2 knuckle epitope peptide via a two-step reaction. Hyaluronic acid was modified to have thiol functional groups to replace the cetyl trimethylammonium bromide ligands on the surface of GNRs. The thiolated peptides were subsequently reacted with hyaluronic acid on the surface on GNRs via a maleimide-hydrazide crosslinker. The conjugation was confirmed by the change of surface charge of GNRs and the plasmon shift. A colorimetric peptide assay suggested more than 69% of the thiolated peptides were conjugated with the hyaluronic acid coated gold nanorods. Moreover, in vitro cell viability showed that BMP-2 conjugated hyaluronic acid functionalized gold nanorods (B2HGR) were cytocompatible and did not cause cytotoxicity to fibroblast cells. The B2HGRs also significantly promote cellular uptake of the BMP-2 peptides in both human mesenchymal stem cells and porcine chondrocytes due to multivalent ligand binding to the BMP receptors on the cell surface resulting in receptor-mediated endocytosis. The enhanced cellular uptake was clearly observed under a confocal microscope resulting in the significant activation of type II collagen gene expression and glucosaminoglycan secretion in those cells. Furthermore, our delivery system is a proof-of-concept of using scaffolds in combination with nanodelivery platform to enhance cartilaginous repair. The peptide loading capacity and the release is not limited by the scaffolds. Therefore, our delivery platform has potential applications for cartilage regeneration in a preclinical and clinical setting in the future. |
| Databáze: | OpenAIRE |
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