Silver Nanoparticles Selectively Treat Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors in a Neurofibromin-Dependent Manner
Neurofibromatosis type 1 (NF1) is among the most common neurogenic disorders, characterized by loss of function mutations in the neurofibromin gene (<i>NF1</i>). NF1 patients are extremely susceptible to developing neurofibromas, which can transform into deadly malignant peripheral nerve...
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MDPI AG
2022-06-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/7/1080 |
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| author | Garrett Alewine Jerrica Knight Adithya Ghantae Christina Mamrega Bashnona Attiah Robert A. Coover Cale D. Fahrenholtz |
| author_facet | Garrett Alewine Jerrica Knight Adithya Ghantae Christina Mamrega Bashnona Attiah Robert A. Coover Cale D. Fahrenholtz |
| author_sort | Garrett Alewine |
| collection | DOAJ |
| description | Neurofibromatosis type 1 (NF1) is among the most common neurogenic disorders, characterized by loss of function mutations in the neurofibromin gene (<i>NF1</i>). NF1 patients are extremely susceptible to developing neurofibromas, which can transform into deadly malignant peripheral nerve sheath tumors (MPNSTs). At the center of these tumors are <i>NF1</i>-null Schwann cells. Here, we found that nanomedicine shows promise in the treatment of NF1-associated MPNSTs. We assessed the cytotoxicity of silver nanoparticles (AgNPs) in <i>NF1</i>-null NF1-associated MPNSTs, <i>NF1</i>-wildtype sporadic MPNST, and normal Schwann cells. Our data show that AgNP are selectivity cytotoxic to NF1-associated MPNSTs relative to sporadic MPNST and Schwann cells. Furthermore, we found that sensitivity to AgNPs is correlated with the expression levels of functional neurofibromin. The restoration of functional neurofibromin in NF1-associated MPNSTs reduces AgNP sensitivity, and the knockdown of neurofibromin in Schwann cells increases AgNP sensitivity. This finding is unique to AgNPs, as <i>NF1</i> restoration does not alter sensitivity to standard of care chemotherapy doxorubicin in NF1-associated MPNSTs. Using an in vitro model system, we then found that AgNP can selectively eradicate NF1-associated MPNSTs in co-culture with Schwann cells at doses tolerable to normal cells. AgNP represents a novel therapy for the treatment of NF1-associated MPNSTs and addresses significant unmet clinical need. |
| first_indexed | 2024-03-09T10:16:37Z |
| format | Article |
| id | doaj.art-ad2690c435334286869c15b3cddea5fa |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T10:16:37Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-ad2690c435334286869c15b3cddea5fa2023-12-01T22:20:33ZengMDPI AGJournal of Personalized Medicine2075-44262022-06-01127108010.3390/jpm12071080Silver Nanoparticles Selectively Treat Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors in a Neurofibromin-Dependent MannerGarrett Alewine0Jerrica Knight1Adithya Ghantae2Christina Mamrega3Bashnona Attiah4Robert A. Coover5Cale D. Fahrenholtz6Department of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC 27268, USADepartment of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC 27268, USADepartment of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC 27268, USADepartment of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC 27268, USADepartment of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC 27268, USADepartment of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC 27268, USADepartment of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC 27268, USANeurofibromatosis type 1 (NF1) is among the most common neurogenic disorders, characterized by loss of function mutations in the neurofibromin gene (<i>NF1</i>). NF1 patients are extremely susceptible to developing neurofibromas, which can transform into deadly malignant peripheral nerve sheath tumors (MPNSTs). At the center of these tumors are <i>NF1</i>-null Schwann cells. Here, we found that nanomedicine shows promise in the treatment of NF1-associated MPNSTs. We assessed the cytotoxicity of silver nanoparticles (AgNPs) in <i>NF1</i>-null NF1-associated MPNSTs, <i>NF1</i>-wildtype sporadic MPNST, and normal Schwann cells. Our data show that AgNP are selectivity cytotoxic to NF1-associated MPNSTs relative to sporadic MPNST and Schwann cells. Furthermore, we found that sensitivity to AgNPs is correlated with the expression levels of functional neurofibromin. The restoration of functional neurofibromin in NF1-associated MPNSTs reduces AgNP sensitivity, and the knockdown of neurofibromin in Schwann cells increases AgNP sensitivity. This finding is unique to AgNPs, as <i>NF1</i> restoration does not alter sensitivity to standard of care chemotherapy doxorubicin in NF1-associated MPNSTs. Using an in vitro model system, we then found that AgNP can selectively eradicate NF1-associated MPNSTs in co-culture with Schwann cells at doses tolerable to normal cells. AgNP represents a novel therapy for the treatment of NF1-associated MPNSTs and addresses significant unmet clinical need.https://www.mdpi.com/2075-4426/12/7/1080nanomedicineoncologysilver nanoparticlesmalignant peripheral nerve sheath tumorsneurofibromatosis type 1 |
| spellingShingle | Garrett Alewine Jerrica Knight Adithya Ghantae Christina Mamrega Bashnona Attiah Robert A. Coover Cale D. Fahrenholtz Silver Nanoparticles Selectively Treat Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors in a Neurofibromin-Dependent Manner Journal of Personalized Medicine nanomedicine oncology silver nanoparticles malignant peripheral nerve sheath tumors neurofibromatosis type 1 |
| title | Silver Nanoparticles Selectively Treat Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors in a Neurofibromin-Dependent Manner |
| title_full | Silver Nanoparticles Selectively Treat Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors in a Neurofibromin-Dependent Manner |
| title_fullStr | Silver Nanoparticles Selectively Treat Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors in a Neurofibromin-Dependent Manner |
| title_full_unstemmed | Silver Nanoparticles Selectively Treat Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors in a Neurofibromin-Dependent Manner |
| title_short | Silver Nanoparticles Selectively Treat Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors in a Neurofibromin-Dependent Manner |
| title_sort | silver nanoparticles selectively treat neurofibromatosis type 1 associated malignant peripheral nerve sheath tumors in a neurofibromin dependent manner |
| topic | nanomedicine oncology silver nanoparticles malignant peripheral nerve sheath tumors neurofibromatosis type 1 |
| url | https://www.mdpi.com/2075-4426/12/7/1080 |
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