期刊
CANCERS
卷 12, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/cancers12040965
关键词
cancer therapy; mesenchymal stem cells; glycoengineering; ovarian cancer; patient-derived xenograft tumor model; two-step tumor targeting
类别
资金
- Minnesota Ovarian Cancer Alliance Research Grant
- National Institute of Health [EB022558]
- Chorzempa Ovarian Cancer Research Fund
- NIH/NCI [P30CA07759821]
- CTSI from NCATS [UL1TR00249402]
- MN Masonic Cancer Center (TWG grant)
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.
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