A cell surface clicked navigation system to direct specific bone targeting

Bioorg Med Chem. 2018 Feb 1;26(3):758-764. doi: 10.1016/j.bmc.2017.12.037. Epub 2017 Dec 26.


Cell therapies are promising up-and-coming therapeutic strategies for many diseases. For maximal therapeutic benefits, injected cells have to navigate their way to a designated area, including organ and tissue; unfortunately, the majority of therapeutic cells are currently administered without a guide or homing device. To improve this serious shortcoming, a functionalization method was developed to equip cells with a homing signal. Its application was demonstrated by applying an Azadibenzocyclooctyne-bisphosphonate (ADIBO-BP) and azide paired bioorthogonal chemistry on cells for bone specific homing. Jurkat T cells and bone marrow derived stromal cells (BMSCs) were cultured with tetraacetylated N-azidoacetyl-d-mannosamine (Ac4ManNAz) to place unnatural azido groups onto the cell's surface; these azido groups were then reacted with ADIBO-BP. The tethered bisphosphonates were able to bring Jurkat cells to hydroxyapatite, the major component of bone, and mineralized SAOS-2 cells. The incorporated BP groups also enhanced the specific affinity of BMSCs to mouse femur bone fragments in vitro. The introduced navigation strategy is expected to have a broad application in cell therapy, because through the biocompatible ADIBO and azide reactive pair, various homing signals could be efficiently anchored onto therapeutic cells.

Keywords: Bioorthogonal chemistry; Bisphosphonate; Bone; Cell homing; Cell therapy.

MeSH terms

  • Animals
  • Azides / chemistry
  • Bone Marrow Cells / cytology
  • Bone and Bones / cytology
  • Bone and Bones / metabolism
  • Cell Differentiation / drug effects*
  • Cell Survival / drug effects
  • Cell- and Tissue-Based Therapy
  • Cells, Cultured
  • Diphosphonates / chemistry
  • Diphosphonates / pharmacology*
  • Durapatite / metabolism
  • Hexosamines / toxicity
  • Humans
  • Jurkat Cells
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence


  • Azides
  • Diphosphonates
  • Hexosamines
  • mannosamine
  • Durapatite