Mesoporous Silica Nanoparticle–Based Combination of NQO1 Inhibitor and 5-Fluorouracil for Potent Antitumor Effect Against Head and Neck Squamous Cell Carcinoma (HNSCC)
Abstract Head and neck squamous cell carcinomas (HNSCC) are one of the deadliest forms of cancer, and 90% of its origin is from squamous cells. NAD(P)H:quinone oxidoreductase 1 (NQO1), an enzyme overexpressed in squamous cell carcinoma, plays an important role in proliferation and chemoresistance. T...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2019-12-01
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| Series: | Nanoscale Research Letters |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s11671-019-3224-3 |
| _version_ | 1797712864468795392 |
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| author | Jing Chen Shuzhen Zhang Shuai Zhang Shanjun Gao Jianbo Wang Dongchun Lei Pengqiang Du Zhiwei Xu Cailiang Zhu Hongbin Sun |
| author_facet | Jing Chen Shuzhen Zhang Shuai Zhang Shanjun Gao Jianbo Wang Dongchun Lei Pengqiang Du Zhiwei Xu Cailiang Zhu Hongbin Sun |
| author_sort | Jing Chen |
| collection | DOAJ |
| description | Abstract Head and neck squamous cell carcinomas (HNSCC) are one of the deadliest forms of cancer, and 90% of its origin is from squamous cells. NAD(P)H:quinone oxidoreductase 1 (NQO1), an enzyme overexpressed in squamous cell carcinoma, plays an important role in proliferation and chemoresistance. The main aims were to study the inhibitory effect of ß-lapachone (ARQ761 in clinical form) in HNSCC and to study the combinational effect of 5-FU and ß-lap in improving the therapeutic efficacy in HNSCC. Lipid bilayer–assembled mesoporous silica nanoparticles loaded with 5-FU/ß-lap were prepared and studied for its physicochemical and biological properties. ß-lap showed a concentration-dependent inhibition of NQO1 enzyme activity in Cal33 cells. Notably, significant inhibitory effect was observed at a dose of 20–50 μg/ml of ß-lap. Combination of 5-FU+ß-lap resulted in lower cell viability; most notably, 5-FU/ß-lap-loaded mesoporous silica nanoparticles (FNQ-MSN) exhibited significantly lower cell viability compared with that of any of the individual drug or physical combinations. ß-lap resulted in a decrease in the protein band of NQO1 compared with control; however, most notable decrease in the NQO1 level was observed in the FNQ-MSN-treated cell group. FNQ-MSN resulted in more than 60% of cell apoptosis (early and late apoptosis) and predominant nuclear fragmentation of cancer cells indicating the superior anticancer effect of a carrier-based combination regimen. Notable decrease in tumor volume was observed with the physical mixture of 5-FU+ß-lap; however, combined treatment of carrier-based 5-FU and ß-lap (FNQ-MSN) significantly delayed the tumor growth and prolonged the survival of tumor-bearing xenograft mice. These findings suggest the potential of NQO1 inhibitor in enhancing the chemotherapeutic potential of 5-FU in the treatment of HNSCC. |
| first_indexed | 2024-03-12T07:28:05Z |
| format | Article |
| id | doaj.art-511c094363dd4a919413adf59365cb68 |
| institution | Directory Open Access Journal |
| issn | 1931-7573 1556-276X |
| language | English |
| last_indexed | 2024-03-12T07:28:05Z |
| publishDate | 2019-12-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Nanoscale Research Letters |
| spelling | doaj.art-511c094363dd4a919413adf59365cb682023-09-02T21:59:06ZengSpringerOpenNanoscale Research Letters1931-75731556-276X2019-12-0114111210.1186/s11671-019-3224-3Mesoporous Silica Nanoparticle–Based Combination of NQO1 Inhibitor and 5-Fluorouracil for Potent Antitumor Effect Against Head and Neck Squamous Cell Carcinoma (HNSCC)Jing Chen0Shuzhen Zhang1Shuai Zhang2Shanjun Gao3Jianbo Wang4Dongchun Lei5Pengqiang Du6Zhiwei Xu7Cailiang Zhu8Hongbin Sun9Department of Dermatology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s HospitalDepartment of Dermatology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s HospitalDepartment of Dermatology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s HospitalMicrobiome Laboratory, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Dermatology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s HospitalDepartment of Dermatology, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s HospitalDepartment of Pharmacy, Henan Provincial People’s HospitalClinical Research Service Center, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s HospitalSchool of Food and Biological Engineering, Zhengzhou University of Light IndustrySchool of Food and Biological Engineering, Zhengzhou University of Light IndustryAbstract Head and neck squamous cell carcinomas (HNSCC) are one of the deadliest forms of cancer, and 90% of its origin is from squamous cells. NAD(P)H:quinone oxidoreductase 1 (NQO1), an enzyme overexpressed in squamous cell carcinoma, plays an important role in proliferation and chemoresistance. The main aims were to study the inhibitory effect of ß-lapachone (ARQ761 in clinical form) in HNSCC and to study the combinational effect of 5-FU and ß-lap in improving the therapeutic efficacy in HNSCC. Lipid bilayer–assembled mesoporous silica nanoparticles loaded with 5-FU/ß-lap were prepared and studied for its physicochemical and biological properties. ß-lap showed a concentration-dependent inhibition of NQO1 enzyme activity in Cal33 cells. Notably, significant inhibitory effect was observed at a dose of 20–50 μg/ml of ß-lap. Combination of 5-FU+ß-lap resulted in lower cell viability; most notably, 5-FU/ß-lap-loaded mesoporous silica nanoparticles (FNQ-MSN) exhibited significantly lower cell viability compared with that of any of the individual drug or physical combinations. ß-lap resulted in a decrease in the protein band of NQO1 compared with control; however, most notable decrease in the NQO1 level was observed in the FNQ-MSN-treated cell group. FNQ-MSN resulted in more than 60% of cell apoptosis (early and late apoptosis) and predominant nuclear fragmentation of cancer cells indicating the superior anticancer effect of a carrier-based combination regimen. Notable decrease in tumor volume was observed with the physical mixture of 5-FU+ß-lap; however, combined treatment of carrier-based 5-FU and ß-lap (FNQ-MSN) significantly delayed the tumor growth and prolonged the survival of tumor-bearing xenograft mice. These findings suggest the potential of NQO1 inhibitor in enhancing the chemotherapeutic potential of 5-FU in the treatment of HNSCC.https://doi.org/10.1186/s11671-019-3224-3Squamous cell carcinomaNQO1 inhibitorLipid bilayerMesoporous silica nanoparticlesApoptosis |
| spellingShingle | Jing Chen Shuzhen Zhang Shuai Zhang Shanjun Gao Jianbo Wang Dongchun Lei Pengqiang Du Zhiwei Xu Cailiang Zhu Hongbin Sun Mesoporous Silica Nanoparticle–Based Combination of NQO1 Inhibitor and 5-Fluorouracil for Potent Antitumor Effect Against Head and Neck Squamous Cell Carcinoma (HNSCC) Nanoscale Research Letters Squamous cell carcinoma NQO1 inhibitor Lipid bilayer Mesoporous silica nanoparticles Apoptosis |
| title | Mesoporous Silica Nanoparticle–Based Combination of NQO1 Inhibitor and 5-Fluorouracil for Potent Antitumor Effect Against Head and Neck Squamous Cell Carcinoma (HNSCC) |
| title_full | Mesoporous Silica Nanoparticle–Based Combination of NQO1 Inhibitor and 5-Fluorouracil for Potent Antitumor Effect Against Head and Neck Squamous Cell Carcinoma (HNSCC) |
| title_fullStr | Mesoporous Silica Nanoparticle–Based Combination of NQO1 Inhibitor and 5-Fluorouracil for Potent Antitumor Effect Against Head and Neck Squamous Cell Carcinoma (HNSCC) |
| title_full_unstemmed | Mesoporous Silica Nanoparticle–Based Combination of NQO1 Inhibitor and 5-Fluorouracil for Potent Antitumor Effect Against Head and Neck Squamous Cell Carcinoma (HNSCC) |
| title_short | Mesoporous Silica Nanoparticle–Based Combination of NQO1 Inhibitor and 5-Fluorouracil for Potent Antitumor Effect Against Head and Neck Squamous Cell Carcinoma (HNSCC) |
| title_sort | mesoporous silica nanoparticle based combination of nqo1 inhibitor and 5 fluorouracil for potent antitumor effect against head and neck squamous cell carcinoma hnscc |
| topic | Squamous cell carcinoma NQO1 inhibitor Lipid bilayer Mesoporous silica nanoparticles Apoptosis |
| url | https://doi.org/10.1186/s11671-019-3224-3 |
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