Glycoengineered mesenchymal stem cells as an enabling platform for two-step targeting of solid tumors

Buddhadev Layek, Tanmoy Sadhukha, Swayam Prabha

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Current tumor targeted drug and diagnostic delivery systems suffer from a lack of selectivity for tumor cells. Here, we propose a two-step tumor targeting strategy based on mesenchymal stem cells (MSCs), which actively traffic to tumors. We developed glycoengineering protocols to induce expression of non-natural azide groups on the surface of MSCs without affecting their viability or tumor homing properties. Glycoengineered MSCs demonstrated active tumor homing in subcutaneous and orthotopic lung and ovarian tumor models. Subsequent systemic administration of dibenzyl cyclooctyne (DBCO)-labeled fluorophores or nanoparticles to MSC pretreated mice resulted in enhanced tumor accumulation of these agents through bio-orthogonal copper-free click chemistry. Further, administration of glycoengineered MSCs along with paclitaxel-loaded DBCO-functionalized nanoparticles resulted in significant (p < 0.05) inhibition of tumor growth and improved survival (p < 0.0001) in an orthotopic metastatic ovarian tumor model. These results provide evidence for the potential of MSC-based two-step targeting strategy to improve the tumor specificity of diagnostic agents and drugs, and thus potentially improve the treatment outcomes for patients diagnosed with cancer.

Original languageEnglish (US)
Pages (from-to)97-109
Number of pages13
JournalBiomaterials
Volume88
DOIs
StatePublished - May 1 2016

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Stem cells
Mesenchymal Stromal Cells
Tumors
Neoplasms
Nanoparticles
Click Chemistry
Azides
Fluorophores
Paclitaxel
Drug Delivery Systems
Pharmaceutical Preparations
Copper
Cells
Lung

Keywords

  • Cancer therapy
  • Click chemistry
  • Glycobiology
  • Imaging
  • Nanoparticles
  • Theranostics
  • Two-step targeting

Cite this

Glycoengineered mesenchymal stem cells as an enabling platform for two-step targeting of solid tumors. / Layek, Buddhadev; Sadhukha, Tanmoy; Prabha, Swayam.

In: Biomaterials, Vol. 88, 01.05.2016, p. 97-109.

Research output: Contribution to journalArticle

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