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...
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| Veröffentlicht in: | Cancers 2020-04, Vol.12 (4), p.965 |
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| creator | Layek, Buddhadev Shetty, Mihir Nethi, Susheel Kumar Sehgal, Drishti Starr, Timothy K Prabha, Swayam |
| 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 (
< 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. |
| doi_str_mv | 10.3390/cancers12040965 |
| format | Article |
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< 0.05) and improved survival in mice receiving MSC-Az along with paclitaxel-loaded DBCO-functionalized nanoparticles compared to controls. 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Shetty, Mihir ; Nethi, Susheel Kumar ; Sehgal, Drishti ; Starr, Timothy K ; Prabha, Swayam</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-e3107814e9e68b1821733189468c352eebe2943876f5d7b4095b6d7714961aec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antitumor activity</topic><topic>Azide</topic><topic>Bioluminescence</topic><topic>Biosynthesis</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Drug delivery</topic><topic>Drug delivery systems</topic><topic>Drug dosages</topic><topic>Feasibility studies</topic><topic>Ligands</topic><topic>Mesenchymal stem cells</topic><topic>Metastases</topic><topic>Nanoparticles</topic><topic>Ovarian cancer</topic><topic>Paclitaxel</topic><topic>Proteins</topic><topic>Retention</topic><topic>Solid tumors</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Xenografts</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Layek, Buddhadev</creatorcontrib><creatorcontrib>Shetty, Mihir</creatorcontrib><creatorcontrib>Nethi, Susheel Kumar</creatorcontrib><creatorcontrib>Sehgal, Drishti</creatorcontrib><creatorcontrib>Starr, Timothy K</creatorcontrib><creatorcontrib>Prabha, Swayam</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Layek, Buddhadev</au><au>Shetty, Mihir</au><au>Nethi, Susheel Kumar</au><au>Sehgal, Drishti</au><au>Starr, Timothy K</au><au>Prabha, Swayam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2020-04-14</date><risdate>2020</risdate><volume>12</volume><issue>4</issue><spage>965</spage><pages>965-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Nanocarriers have been extensively utilized for the systemic targeting of various solid tumors and their metastases. 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< 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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32295145</pmid><doi>10.3390/cancers12040965</doi><orcidid>https://orcid.org/0000-0002-9812-0515</orcidid><orcidid>https://orcid.org/0000-0002-6308-3451</orcidid><orcidid>https://orcid.org/0000-0002-2457-7619</orcidid><orcidid>https://orcid.org/0000-0002-4138-1618</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Antitumor activity Azide Bioluminescence Biosynthesis Cancer therapies Chemotherapy Drug delivery Drug delivery systems Drug dosages Feasibility studies Ligands Mesenchymal stem cells Metastases Nanoparticles Ovarian cancer Paclitaxel Proteins Retention Solid tumors Stem cell transplantation Stem cells Tumor cells Tumors Xenografts |
| title | Mesenchymal Stem Cells As Guideposts for Nanoparticle-Mediated Targeted Drug Delivery in Ovarian Cancer |
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