Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth
Abstract By exploiting the self‐therapeutic properties of gold nanoparticles (GNPs) a molecular axis that promotes the growth of high‐grade serous ovarian cancer (HGSOC), one of the deadliest gynecologic malignancies with poorly understood underlying molecular mechanisms, has been identified. The bi...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-11-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202200491 |
| _version_ | 1811192820965310464 |
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| author | Md. Nazir Hossen Lin Wang Shailendra Kumar Dhar Dwivedi Yushan Zhang Geeta Rao Chandra Kumar Elechalwar Vinit Sheth Anindya Dey Sima Asfa Suresh Kumar Gulla Chao Xu Kar‐Ming Fung J. David Robertson Magdalena Bieniasz Stefan Wilhelm Resham Bhattacharya Priyabrata Mukherjee |
| author_facet | Md. Nazir Hossen Lin Wang Shailendra Kumar Dhar Dwivedi Yushan Zhang Geeta Rao Chandra Kumar Elechalwar Vinit Sheth Anindya Dey Sima Asfa Suresh Kumar Gulla Chao Xu Kar‐Ming Fung J. David Robertson Magdalena Bieniasz Stefan Wilhelm Resham Bhattacharya Priyabrata Mukherjee |
| author_sort | Md. Nazir Hossen |
| collection | DOAJ |
| description | Abstract By exploiting the self‐therapeutic properties of gold nanoparticles (GNPs) a molecular axis that promotes the growth of high‐grade serous ovarian cancer (HGSOC), one of the deadliest gynecologic malignancies with poorly understood underlying molecular mechanisms, has been identified. The biodistribution and toxicity of GNPs administered by intravenous or intraperitoneal injection, both as a single dose or by repeated dosing over two weeks are first assessed; no biochemical or histological toxicity to vital organs is found. Using an orthotopic patient‐derived xenograft (PDX) model of HGSOC, the authors then show that GNP treatment robustly inhibits tumor growth. Investigating the molecular mechanisms underlying the GNP efficacy reveals that GNPs downregulate insulin growth factor binding protein 2 (IGFBP2) by disrupting its autoregulation via the IGFBP2/mTOR/PTEN axis. This mechanism is validated by treating a cell line‐based human xenograft tumor with GNPs and an mTOR dual‐kinase inhibitor (PI‐103), either individually or in combination with GNPs; GNP and PI‐103 combination therapy inhibit ovarian tumor growth similarly to GNPs alone. This report illustrates how the self‐therapeutic properties of GNPs can be exploited as a discovery tool to identify a critical signaling axis responsible for poor prognosis in ovarian cancer and provides an opportunity to interrogate the axis to improve patient outcomes. |
| first_indexed | 2024-04-11T23:57:45Z |
| format | Article |
| id | doaj.art-afa0d0c72dab4dba82ca7006fafd0dee |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-11T23:57:45Z |
| publishDate | 2022-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-afa0d0c72dab4dba82ca7006fafd0dee2022-12-22T03:56:19ZengWileyAdvanced Science2198-38442022-11-01931n/an/a10.1002/advs.202200491Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer GrowthMd. Nazir Hossen0Lin Wang1Shailendra Kumar Dhar Dwivedi2Yushan Zhang3Geeta Rao4Chandra Kumar Elechalwar5Vinit Sheth6Anindya Dey7Sima Asfa8Suresh Kumar Gulla9Chao Xu10Kar‐Ming Fung11J. David Robertson12Magdalena Bieniasz13Stefan Wilhelm14Resham Bhattacharya15Priyabrata Mukherjee16Peggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAAging and Metabolism Research Program Oklahoma Medical Research Foundation Oklahoma City OK 73104 USAPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAStephenson School of Biomedical Engineering University of Oklahoma Norman Oklahoma 73019 USADepartment of Obstetrics and Gynecology University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USADepartment of Chemistry and University of Missouri Research Reactor University of Missouri Columbia Missouri 65211 United StatesPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAPeggy and Charles Stephenson Cancer Center University of Oklahoma Health Science Center Oklahoma City Oklahoma 73104 USAAbstract By exploiting the self‐therapeutic properties of gold nanoparticles (GNPs) a molecular axis that promotes the growth of high‐grade serous ovarian cancer (HGSOC), one of the deadliest gynecologic malignancies with poorly understood underlying molecular mechanisms, has been identified. The biodistribution and toxicity of GNPs administered by intravenous or intraperitoneal injection, both as a single dose or by repeated dosing over two weeks are first assessed; no biochemical or histological toxicity to vital organs is found. Using an orthotopic patient‐derived xenograft (PDX) model of HGSOC, the authors then show that GNP treatment robustly inhibits tumor growth. Investigating the molecular mechanisms underlying the GNP efficacy reveals that GNPs downregulate insulin growth factor binding protein 2 (IGFBP2) by disrupting its autoregulation via the IGFBP2/mTOR/PTEN axis. This mechanism is validated by treating a cell line‐based human xenograft tumor with GNPs and an mTOR dual‐kinase inhibitor (PI‐103), either individually or in combination with GNPs; GNP and PI‐103 combination therapy inhibit ovarian tumor growth similarly to GNPs alone. This report illustrates how the self‐therapeutic properties of GNPs can be exploited as a discovery tool to identify a critical signaling axis responsible for poor prognosis in ovarian cancer and provides an opportunity to interrogate the axis to improve patient outcomes.https://doi.org/10.1002/advs.202200491gold nanoparticlesIGFBP2IGFBP2/PTEN autoregulationovarian cancertumor therapy |
| spellingShingle | Md. Nazir Hossen Lin Wang Shailendra Kumar Dhar Dwivedi Yushan Zhang Geeta Rao Chandra Kumar Elechalwar Vinit Sheth Anindya Dey Sima Asfa Suresh Kumar Gulla Chao Xu Kar‐Ming Fung J. David Robertson Magdalena Bieniasz Stefan Wilhelm Resham Bhattacharya Priyabrata Mukherjee Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth Advanced Science gold nanoparticles IGFBP2 IGFBP2/PTEN autoregulation ovarian cancer tumor therapy |
| title | Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth |
| title_full | Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth |
| title_fullStr | Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth |
| title_full_unstemmed | Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth |
| title_short | Gold Nanoparticles Disrupt the IGFBP2/mTOR/PTEN Axis to Inhibit Ovarian Cancer Growth |
| title_sort | gold nanoparticles disrupt the igfbp2 mtor pten axis to inhibit ovarian cancer growth |
| topic | gold nanoparticles IGFBP2 IGFBP2/PTEN autoregulation ovarian cancer tumor therapy |
| url | https://doi.org/10.1002/advs.202200491 |
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