Mesenchymal stem cells as guideposts for nanoparticle-mediated targeted drug delivery in ovarian cancer

Buddhadev Layek, Mihir Shetty, Susheel Kumar Nethi, Drishti Sehgal, Timothy K. Starr, Swayam Prabha

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Nanocarriers have been extensively utilized for the systemic targeting of various solid tumors and their metastases. However, current drug delivery systems, in general, suffer from a lack of selectivity for tumor cells. Here, we develop a novel two-step targeting strategy that relies on the selective accumulation of targetable synthetic receptors (i.e., azide moieties) in tumor tissues, followed by delivery of drug-loaded nanoparticles having a high binding affinity for these receptors. Mesenchymal stem cells (MSCs) were used as vehicles for the tumor-specific accumulation of azide moieties, while dibenzyl cyclooctyne (DBCO) was used as the targeting ligand. Biodistribution and antitumor efficacy studies were performed in both orthotopic metastatic and patient-derived xenograft (PDX) tumor models of ovarian cancer. Our studies show that nanoparticles are retained in tumors at a significantly higher concentration in mice that received azide-labeled MSCs (MSC-Az). Furthermore, we observed significantly reduced tumor growth (p < 0.05) and improved survival in mice receiving MSC-Az along with paclitaxel-loaded DBCO-functionalized nanoparticles compared to controls. These studies demonstrate the feasibility of a two-step targeting strategy for efficient delivery of concentrated chemotherapy for treating solid tumors.

Original languageEnglish (US)
Article number965
JournalCancers
Volume12
Issue number4
DOIs
StatePublished - Apr 2020

Keywords

  • Cancer therapy
  • Glycoengineering
  • Mesenchymal stem cells
  • Ovarian cancer
  • Patient-derived xenograft tumor model
  • Two-step tumor targeting

PubMed: MeSH publication types

  • Journal Article

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