Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo
Abstract Silver nanoparticles (AgNPs) show promise for treatment of aggressive cancers including triple‐negative breast cancer (TNBC) in preclinical cancer models. For clinical development of AgNP‐based therapeutics, it will be necessary to clearly define the specific physicochemical features of the...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-10-01
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| Series: | FASEB BioAdvances |
| Subjects: | |
| Online Access: | https://doi.org/10.1096/fba.2019-00021 |
| _version_ | 1818945872892788736 |
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| author | Jessica Swanner Cale D. Fahrenholtz Iliana Tenvooren Brian W. Bernish James J. Sears Allison Hooker Cristina M. Furdui Elizabeth Alli Wencheng Li George L. Donati Katherine L. Cook Pierre‐Alexandre Vidi Ravi Singh |
| author_facet | Jessica Swanner Cale D. Fahrenholtz Iliana Tenvooren Brian W. Bernish James J. Sears Allison Hooker Cristina M. Furdui Elizabeth Alli Wencheng Li George L. Donati Katherine L. Cook Pierre‐Alexandre Vidi Ravi Singh |
| author_sort | Jessica Swanner |
| collection | DOAJ |
| description | Abstract Silver nanoparticles (AgNPs) show promise for treatment of aggressive cancers including triple‐negative breast cancer (TNBC) in preclinical cancer models. For clinical development of AgNP‐based therapeutics, it will be necessary to clearly define the specific physicochemical features of the nanoparticles that will be used, and to tie these properties to biological outcomes. To fill this knowledge gap, we performed thorough structure/function, mechanistic, safety, and efficacy studies to assess the potential for AgNPs to treat TNBC. We establish that AgNPs, regardless of size, shape, or stabilizing agent, are highly cytotoxic to TNBC cells at doses that are not cytotoxic to non‐malignant breast epithelial cells. In contrast, TNBC cells and non‐malignant breast epithelial cells are similarly sensitive to exposure to silver cation (Ag+), indicating that the nanoparticle formulation is essential for the TNBC‐specific cytotoxicity. Mechanistically, AgNPs are internalized by both TNBC and non‐malignant breast cells, but are rapidly degraded only in TNBC cells. Exposure to AgNPs depletes cellular antioxidants and causes endoplasmic reticulum stress in TNBC cells without causing similar damage in non‐malignant breast epithelial cells. AgNPs also cause extensive DNA damage in 3D TNBC tumor nodules in vitro, but do not disrupt the normal architecture of breast acini in 3D cell culture, nor cause DNA damage or induce apoptosis in these structures. Lastly, we show that systemically administered AgNPs are effective at non‐toxic doses for reducing the growth of TNBC tumor xenografts in mice. This work provides a rationale for development of AgNPs as a safe and specific TNBC treatment. |
| first_indexed | 2024-12-20T08:06:01Z |
| format | Article |
| id | doaj.art-08194cb37e6d42569e52b2e97a9fcfdd |
| institution | Directory Open Access Journal |
| issn | 2573-9832 |
| language | English |
| last_indexed | 2024-12-20T08:06:01Z |
| publishDate | 2019-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | FASEB BioAdvances |
| spelling | doaj.art-08194cb37e6d42569e52b2e97a9fcfdd2022-12-21T19:47:25ZengWileyFASEB BioAdvances2573-98322019-10-0111063966010.1096/fba.2019-00021Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivoJessica Swanner0Cale D. Fahrenholtz1Iliana Tenvooren2Brian W. Bernish3James J. Sears4Allison Hooker5Cristina M. Furdui6Elizabeth Alli7Wencheng Li8George L. Donati9Katherine L. Cook10Pierre‐Alexandre Vidi11Ravi Singh12Department of Cancer Biology Wake Forest School of Medicine Winston Salem NC USADepartment of Cancer Biology Wake Forest School of Medicine Winston Salem NC USADepartment of Cancer Biology Wake Forest School of Medicine Winston Salem NC USADepartment of Cancer Biology Wake Forest School of Medicine Winston Salem NC USADepartment of Cancer Biology Wake Forest School of Medicine Winston Salem NC USASalem College Winston Salem NC USADepartment of Internal Medicine Section on Molecular Medicine Wake Forest School of Medicine Winston‐Salem NC USADepartment of Cancer Biology Wake Forest School of Medicine Winston Salem NC USADepartment of Pathology Wake Forest School of Medicine Winston‐Salem NC USADepartment of Chemistry Wake Forest University Winston‐Salem NC USADepartment of Surgery Wake Forest School of Medicine Winston‐Salem NC USADepartment of Cancer Biology Wake Forest School of Medicine Winston Salem NC USADepartment of Cancer Biology Wake Forest School of Medicine Winston Salem NC USAAbstract Silver nanoparticles (AgNPs) show promise for treatment of aggressive cancers including triple‐negative breast cancer (TNBC) in preclinical cancer models. For clinical development of AgNP‐based therapeutics, it will be necessary to clearly define the specific physicochemical features of the nanoparticles that will be used, and to tie these properties to biological outcomes. To fill this knowledge gap, we performed thorough structure/function, mechanistic, safety, and efficacy studies to assess the potential for AgNPs to treat TNBC. We establish that AgNPs, regardless of size, shape, or stabilizing agent, are highly cytotoxic to TNBC cells at doses that are not cytotoxic to non‐malignant breast epithelial cells. In contrast, TNBC cells and non‐malignant breast epithelial cells are similarly sensitive to exposure to silver cation (Ag+), indicating that the nanoparticle formulation is essential for the TNBC‐specific cytotoxicity. Mechanistically, AgNPs are internalized by both TNBC and non‐malignant breast cells, but are rapidly degraded only in TNBC cells. Exposure to AgNPs depletes cellular antioxidants and causes endoplasmic reticulum stress in TNBC cells without causing similar damage in non‐malignant breast epithelial cells. AgNPs also cause extensive DNA damage in 3D TNBC tumor nodules in vitro, but do not disrupt the normal architecture of breast acini in 3D cell culture, nor cause DNA damage or induce apoptosis in these structures. Lastly, we show that systemically administered AgNPs are effective at non‐toxic doses for reducing the growth of TNBC tumor xenografts in mice. This work provides a rationale for development of AgNPs as a safe and specific TNBC treatment.https://doi.org/10.1096/fba.2019-00021DNA damagenanomedicineredoxtoxicityunfolded protein response |
| spellingShingle | Jessica Swanner Cale D. Fahrenholtz Iliana Tenvooren Brian W. Bernish James J. Sears Allison Hooker Cristina M. Furdui Elizabeth Alli Wencheng Li George L. Donati Katherine L. Cook Pierre‐Alexandre Vidi Ravi Singh Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo FASEB BioAdvances DNA damage nanomedicine redox toxicity unfolded protein response |
| title | Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo |
| title_full | Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo |
| title_fullStr | Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo |
| title_full_unstemmed | Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo |
| title_short | Silver nanoparticles selectively treat triple‐negative breast cancer cells without affecting non‐malignant breast epithelial cells in vitro and in vivo |
| title_sort | silver nanoparticles selectively treat triple negative breast cancer cells without affecting non malignant breast epithelial cells in vitro and in vivo |
| topic | DNA damage nanomedicine redox toxicity unfolded protein response |
| url | https://doi.org/10.1096/fba.2019-00021 |
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