Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer
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 selectiv...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/4/965 |
| _version_ | 1797570690029715456 |
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| author | Buddhadev Layek Mihir Shetty Susheel Kumar Nethi Drishti Sehgal Timothy K. Starr Swayam Prabha |
| author_facet | Buddhadev Layek Mihir Shetty Susheel Kumar Nethi Drishti Sehgal Timothy K. Starr Swayam Prabha |
| author_sort | Buddhadev Layek |
| collection | DOAJ |
| description | 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 (<i>p</i> < 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. |
| first_indexed | 2024-03-10T20:28:44Z |
| format | Article |
| id | doaj.art-16f87f55a1f54de291bd4922d78d6ed8 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T20:28:44Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-16f87f55a1f54de291bd4922d78d6ed82023-11-19T21:33:08ZengMDPI AGCancers2072-66942020-04-0112496510.3390/cancers12040965Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian CancerBuddhadev Layek0Mihir Shetty1Susheel Kumar Nethi2Drishti Sehgal3Timothy K. Starr4Swayam Prabha5Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USADepartment of Obstetrics, Gynecology and Women’s Health (OBGYN), University of Minnesota, Minneapolis, MN 55455, USADepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USASchool of Pharmacy, Temple University, Philadelphia, PA 19140, USADepartment of Obstetrics, Gynecology and Women’s Health (OBGYN), University of Minnesota, Minneapolis, MN 55455, USADepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USANanocarriers 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 (<i>p</i> < 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.https://www.mdpi.com/2072-6694/12/4/965cancer therapymesenchymal stem cellsglycoengineeringovarian cancerpatient-derived xenograft tumor modeltwo-step tumor targeting |
| spellingShingle | Buddhadev Layek Mihir Shetty Susheel Kumar Nethi Drishti Sehgal Timothy K. Starr Swayam Prabha Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer Cancers cancer therapy mesenchymal stem cells glycoengineering ovarian cancer patient-derived xenograft tumor model two-step tumor targeting |
| title | Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer |
| title_full | Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer |
| title_fullStr | Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer |
| title_full_unstemmed | Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer |
| title_short | Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer |
| title_sort | mesenchymal stem cells as guideposts for nanoparticle mediated targeted drug delivery in ovarian cancer |
| topic | cancer therapy mesenchymal stem cells glycoengineering ovarian cancer patient-derived xenograft tumor model two-step tumor targeting |
| url | https://www.mdpi.com/2072-6694/12/4/965 |
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