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Gold nanoparticles conjugated with anti-CD133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting

The enhanced permeability and retention effect allows for passive targeting of solid tumours by nanoparticles carrying anticancer drugs. However, active targeting by incorporation of various ligands onto nanoparticles can provide for a more selective and enhanced chemotherapeutic effect and compleme...

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Autores principales: Mohd-Zahid, Manali Haniti, Zulkifli, Siti Nadiah, Che Abdullah, Che Azurahanim, Lim, JitKang, Fakurazi, Sharida, Wong, Kah Keng, Zakaria, Andee Dzulkarnaen, Ismail, Norzila, Uskoković, Vuk, Mohamud, Rohimah, Z. A, Iskandar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030463/
https://www.ncbi.nlm.nih.gov/pubmed/35481195
http://dx.doi.org/10.1039/d1ra01093j
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author Mohd-Zahid, Manali Haniti
Zulkifli, Siti Nadiah
Che Abdullah, Che Azurahanim
Lim, JitKang
Fakurazi, Sharida
Wong, Kah Keng
Zakaria, Andee Dzulkarnaen
Ismail, Norzila
Uskoković, Vuk
Mohamud, Rohimah
Z. A, Iskandar
author_facet Mohd-Zahid, Manali Haniti
Zulkifli, Siti Nadiah
Che Abdullah, Che Azurahanim
Lim, JitKang
Fakurazi, Sharida
Wong, Kah Keng
Zakaria, Andee Dzulkarnaen
Ismail, Norzila
Uskoković, Vuk
Mohamud, Rohimah
Z. A, Iskandar
author_sort Mohd-Zahid, Manali Haniti
collection PubMed
description The enhanced permeability and retention effect allows for passive targeting of solid tumours by nanoparticles carrying anticancer drugs. However, active targeting by incorporation of various ligands onto nanoparticles can provide for a more selective and enhanced chemotherapeutic effect and complement the deficiencies of the passive targeting approach. Here we report on the design of the carboxyl-terminated PEGylated gold nanoparticles (AuNPs), their functionalization with anti-CD133 monoclonal antibody (mAb) via a crosslinking reaction, and subsequent 5-fluorouracil (5-FU) drug loading. The synthesized products in the form of stable colloids were characterised using a range of physicochemical techniques, including X-ray diffraction (XRD), UV-Vis spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Conjugation of anti-CD133 mAb onto PEGylated AuNPs was confirmed with the use of UV-Vis, BCA protein assay and fluorescence microscopy. HCT116 colorectal cancer cells abundantly expressed CD133: 92.4 ± 1.3%, as measured by flow cytometry. Whereas PEGylated AuNPs not conjugated with anti-CD133 mAb accumulated mainly at the cellular membrane, nanoparticles conjugated with anti-CD133 mAb were contained within the nuclear region of the cells. Anti-CD133 mAb conjugation facilitated the specific intracellular uptake due to specific antigen–antibody binding interaction. In vitro cytotoxicity studies on HCT116 cells showed that PEGylated AuNPs and PEGylated AuNPs-CD133 did not elicit any toxicity at any of the tested concentrations. Meanwhile, 5-FU-PEGylated AuNPs-CD133 significantly reduced the cell viability relative to the treatment with 5-FU-PEGylated AuNPs without anti-CD133 mAb conjugates (p < 0.0001). This study shows that the conjugation of nanocarriers with the anti-CD133 antibody improves the specific targeting of 5-FU against colorectal cancer cells. These results demonstrate that simultaneous functionalisation of PEGylated AuNPs with antibodies and chemotherapeutic drugs is a viable strategy to combat cancer through targeted drug delivery.
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spelling pubmed-90304632022-04-26 Gold nanoparticles conjugated with anti-CD133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting Mohd-Zahid, Manali Haniti Zulkifli, Siti Nadiah Che Abdullah, Che Azurahanim Lim, JitKang Fakurazi, Sharida Wong, Kah Keng Zakaria, Andee Dzulkarnaen Ismail, Norzila Uskoković, Vuk Mohamud, Rohimah Z. A, Iskandar RSC Adv Chemistry The enhanced permeability and retention effect allows for passive targeting of solid tumours by nanoparticles carrying anticancer drugs. However, active targeting by incorporation of various ligands onto nanoparticles can provide for a more selective and enhanced chemotherapeutic effect and complement the deficiencies of the passive targeting approach. Here we report on the design of the carboxyl-terminated PEGylated gold nanoparticles (AuNPs), their functionalization with anti-CD133 monoclonal antibody (mAb) via a crosslinking reaction, and subsequent 5-fluorouracil (5-FU) drug loading. The synthesized products in the form of stable colloids were characterised using a range of physicochemical techniques, including X-ray diffraction (XRD), UV-Vis spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Conjugation of anti-CD133 mAb onto PEGylated AuNPs was confirmed with the use of UV-Vis, BCA protein assay and fluorescence microscopy. HCT116 colorectal cancer cells abundantly expressed CD133: 92.4 ± 1.3%, as measured by flow cytometry. Whereas PEGylated AuNPs not conjugated with anti-CD133 mAb accumulated mainly at the cellular membrane, nanoparticles conjugated with anti-CD133 mAb were contained within the nuclear region of the cells. Anti-CD133 mAb conjugation facilitated the specific intracellular uptake due to specific antigen–antibody binding interaction. In vitro cytotoxicity studies on HCT116 cells showed that PEGylated AuNPs and PEGylated AuNPs-CD133 did not elicit any toxicity at any of the tested concentrations. Meanwhile, 5-FU-PEGylated AuNPs-CD133 significantly reduced the cell viability relative to the treatment with 5-FU-PEGylated AuNPs without anti-CD133 mAb conjugates (p < 0.0001). This study shows that the conjugation of nanocarriers with the anti-CD133 antibody improves the specific targeting of 5-FU against colorectal cancer cells. These results demonstrate that simultaneous functionalisation of PEGylated AuNPs with antibodies and chemotherapeutic drugs is a viable strategy to combat cancer through targeted drug delivery. The Royal Society of Chemistry 2021-04-30 /pmc/articles/PMC9030463/ /pubmed/35481195 http://dx.doi.org/10.1039/d1ra01093j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Mohd-Zahid, Manali Haniti
Zulkifli, Siti Nadiah
Che Abdullah, Che Azurahanim
Lim, JitKang
Fakurazi, Sharida
Wong, Kah Keng
Zakaria, Andee Dzulkarnaen
Ismail, Norzila
Uskoković, Vuk
Mohamud, Rohimah
Z. A, Iskandar
Gold nanoparticles conjugated with anti-CD133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting
title Gold nanoparticles conjugated with anti-CD133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting
title_full Gold nanoparticles conjugated with anti-CD133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting
title_fullStr Gold nanoparticles conjugated with anti-CD133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting
title_full_unstemmed Gold nanoparticles conjugated with anti-CD133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting
title_short Gold nanoparticles conjugated with anti-CD133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting
title_sort gold nanoparticles conjugated with anti-cd133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030463/
https://www.ncbi.nlm.nih.gov/pubmed/35481195
http://dx.doi.org/10.1039/d1ra01093j
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