Anti-Tumor Activity of Novel Nimotuzumab-Functionalized Gold Nanoparticles as a Potential Immunotherapeutic Agent against Skin and Lung Cancers
The epidermal growth factor receptor (EGFR) is vital for many different types of cancer. Nimotuzumab (NmAb), an anti-EGFR monoclonal antibody (mAb), is used against some of EGFR-overexpressed cancers in various countries. It targets malignant cells and is internalized via receptor-mediated endocytos...
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MDPI AG
2023-08-01
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| Series: | Journal of Functional Biomaterials |
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| Online Access: | https://www.mdpi.com/2079-4983/14/8/407 |
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| author | Mohammad Anisuzzman Varsha Komalla Mariam Abdulaziz M. Tarkistani Veysel Kayser |
| author_facet | Mohammad Anisuzzman Varsha Komalla Mariam Abdulaziz M. Tarkistani Veysel Kayser |
| author_sort | Mohammad Anisuzzman |
| collection | DOAJ |
| description | The epidermal growth factor receptor (EGFR) is vital for many different types of cancer. Nimotuzumab (NmAb), an anti-EGFR monoclonal antibody (mAb), is used against some of EGFR-overexpressed cancers in various countries. It targets malignant cells and is internalized via receptor-mediated endocytosis. We hypothesized that mAb-nanoparticle conjugation would provide an enhanced therapeutic efficacy, and hence we conjugated NmAb with 27 nm spherical gold nanoparticles (AuNPs) to form AuNP-NmAb nanoconjugates. Using biophysical and spectroscopic methods, including ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and Fourier-transform infrared spectroscopy (FTIR), the AuNP-NmAb complex was characterized. Furthermore, in vitro studies were performed using a medium-level EGFR-expressing skin cancer cell (A431, EGFR<sup>medium</sup>) and low-level EGFR-expressing lung cancer cell (A549, EGFR<sup>low</sup>) to evaluate anti-tumor and cellular uptake efficiency via MTT assay and single-particle inductively coupled plasma mass spectrometry (spICP-MS), respectively. In comparison to NmAb monotherapy, the AuNP-NmAb treatment drastically reduced cancer cell survivability: for A431 cells, the IC<sub>50</sub> value of AuNP-NmAb conjugate was 142.7 µg/mL, while the IC<sub>50</sub> value of free NmAb was 561.3 µg/mL. For A549 cells, the IC<sub>50</sub> value of the AuNP-NmAb conjugate was 163.6 µg/mL, while the IC<sub>50</sub> value of free NmAb was 1,082.0 µg/mL. Therefore, this study highlights the unique therapeutic potential of AuNP-NmAb in EGFR+ cancers and shows the potential to develop other mAb nanoparticle complexes for a superior therapeutic efficacy. |
| first_indexed | 2024-03-10T23:50:10Z |
| format | Article |
| id | doaj.art-247ee59891eb4947a897942acddfc935 |
| institution | Directory Open Access Journal |
| issn | 2079-4983 |
| language | English |
| last_indexed | 2024-03-10T23:50:10Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Functional Biomaterials |
| spelling | doaj.art-247ee59891eb4947a897942acddfc9352023-11-19T01:43:03ZengMDPI AGJournal of Functional Biomaterials2079-49832023-08-0114840710.3390/jfb14080407Anti-Tumor Activity of Novel Nimotuzumab-Functionalized Gold Nanoparticles as a Potential Immunotherapeutic Agent against Skin and Lung CancersMohammad Anisuzzman0Varsha Komalla1Mariam Abdulaziz M. Tarkistani2Veysel Kayser3Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaSydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaSydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaSydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, AustraliaThe epidermal growth factor receptor (EGFR) is vital for many different types of cancer. Nimotuzumab (NmAb), an anti-EGFR monoclonal antibody (mAb), is used against some of EGFR-overexpressed cancers in various countries. It targets malignant cells and is internalized via receptor-mediated endocytosis. We hypothesized that mAb-nanoparticle conjugation would provide an enhanced therapeutic efficacy, and hence we conjugated NmAb with 27 nm spherical gold nanoparticles (AuNPs) to form AuNP-NmAb nanoconjugates. Using biophysical and spectroscopic methods, including ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and Fourier-transform infrared spectroscopy (FTIR), the AuNP-NmAb complex was characterized. Furthermore, in vitro studies were performed using a medium-level EGFR-expressing skin cancer cell (A431, EGFR<sup>medium</sup>) and low-level EGFR-expressing lung cancer cell (A549, EGFR<sup>low</sup>) to evaluate anti-tumor and cellular uptake efficiency via MTT assay and single-particle inductively coupled plasma mass spectrometry (spICP-MS), respectively. In comparison to NmAb monotherapy, the AuNP-NmAb treatment drastically reduced cancer cell survivability: for A431 cells, the IC<sub>50</sub> value of AuNP-NmAb conjugate was 142.7 µg/mL, while the IC<sub>50</sub> value of free NmAb was 561.3 µg/mL. For A549 cells, the IC<sub>50</sub> value of the AuNP-NmAb conjugate was 163.6 µg/mL, while the IC<sub>50</sub> value of free NmAb was 1,082.0 µg/mL. Therefore, this study highlights the unique therapeutic potential of AuNP-NmAb in EGFR+ cancers and shows the potential to develop other mAb nanoparticle complexes for a superior therapeutic efficacy.https://www.mdpi.com/2079-4983/14/8/407nimotuzumabgold nanoparticlenanoconjugatestarget drug deliverycellular uptakecell viability |
| spellingShingle | Mohammad Anisuzzman Varsha Komalla Mariam Abdulaziz M. Tarkistani Veysel Kayser Anti-Tumor Activity of Novel Nimotuzumab-Functionalized Gold Nanoparticles as a Potential Immunotherapeutic Agent against Skin and Lung Cancers Journal of Functional Biomaterials nimotuzumab gold nanoparticle nanoconjugates target drug delivery cellular uptake cell viability |
| title | Anti-Tumor Activity of Novel Nimotuzumab-Functionalized Gold Nanoparticles as a Potential Immunotherapeutic Agent against Skin and Lung Cancers |
| title_full | Anti-Tumor Activity of Novel Nimotuzumab-Functionalized Gold Nanoparticles as a Potential Immunotherapeutic Agent against Skin and Lung Cancers |
| title_fullStr | Anti-Tumor Activity of Novel Nimotuzumab-Functionalized Gold Nanoparticles as a Potential Immunotherapeutic Agent against Skin and Lung Cancers |
| title_full_unstemmed | Anti-Tumor Activity of Novel Nimotuzumab-Functionalized Gold Nanoparticles as a Potential Immunotherapeutic Agent against Skin and Lung Cancers |
| title_short | Anti-Tumor Activity of Novel Nimotuzumab-Functionalized Gold Nanoparticles as a Potential Immunotherapeutic Agent against Skin and Lung Cancers |
| title_sort | anti tumor activity of novel nimotuzumab functionalized gold nanoparticles as a potential immunotherapeutic agent against skin and lung cancers |
| topic | nimotuzumab gold nanoparticle nanoconjugates target drug delivery cellular uptake cell viability |
| url | https://www.mdpi.com/2079-4983/14/8/407 |
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