Bone Targeted Delivery of SDF-1 via Alendronate Functionalized Nanoparticles in Guiding Stem Cell Migration

ACS Appl Mater Interfaces. 2018 Jul 18;10(28):23700-23710. doi: 10.1021/acsami.8b08606. Epub 2018 Jul 6.

Abstract

Stem cells are well-known for their great capacity for tissue regeneration. This provides a promising source for cell-based therapies in treating various bone degenerative disorders. However, the major hurdles for their application in transplantation are the poor bone marrow homing and engraftment efficiencies. Stromal cell-derived factor 1 (SDF-1) has been identified as a major stem cell homing factor. With the aims of bone targeted SDF-1 delivery and regulating MSCs migration, alendronate modified liposomal nanoparticles (Aln-Lipo) carrying SDF-1 gene were developed in this study. Alendronate modification significantly increased the mineral binding affinity of liposomes, and facilitated the gene delivery to osteoblastic cells. Up-regulated SDF-1 expression in osteoblasts triggered MSCs migration. Systemic infusion of Aln-Lipo-SDF-1 with fluorescence labeling in mice showed the accumulation in osseous tissue by biophotonic imaging. Corresponding to the delivered SDF-1, the transplanted GFP+ MSCs were attracted to bone marrow and contributed to bone regeneration. This study may provide a useful technique in regulating stem cell migration.

Keywords: SDF-1; bone targeting; gene delivery; osteoporosis therapy; stem cell homing.

MeSH terms

  • Alendronate
  • Animals
  • Bone and Bones
  • Cell Movement*
  • Chemokine CXCL12
  • Mesenchymal Stem Cells
  • Mice
  • Nanoparticles
  • Stem Cells

Substances

  • Chemokine CXCL12
  • Alendronate