Use of Biocompatible Sorafenib-gold Nanoconjugates for Reversal of Drug Resistance in Human Hepatoblatoma Cells

Abstract The present study identifies the potential of highly biocompatible SF-GNP nano-conjugate to enhance the chemotherapeutic response to combat drug resistance in cancer cells. We developed a stable colloidal suspension of sorafenib-gold nanoconjugate (SF-GNP) of <10 nm size in aqueous mediu...

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Autores principales: Sandeep Kumar Vishwakarma, Priyanka Sharmila, Avinash Bardia, Lakkireddy Chandrakala, N. Raju, G. Sravani, B. V. S. Sastry, Md Aejaz Habeeb, Aleem Ahmed Khan, Marshal Dhayal
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:d0e4b84a554d47299fdab6cb2a459a2a2021-12-02T12:32:39ZUse of Biocompatible Sorafenib-gold Nanoconjugates for Reversal of Drug Resistance in Human Hepatoblatoma Cells10.1038/s41598-017-08878-y2045-2322https://doaj.org/article/d0e4b84a554d47299fdab6cb2a459a2a2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08878-yhttps://doaj.org/toc/2045-2322Abstract The present study identifies the potential of highly biocompatible SF-GNP nano-conjugate to enhance the chemotherapeutic response to combat drug resistance in cancer cells. We developed a stable colloidal suspension of sorafenib-gold nanoconjugate (SF-GNP) of <10 nm size in aqueous medium for reverting the cancer drug resistance in SF-resistant HepG2 cells in a 3D ex-vivo model system. In-vivo biocompatibility assay of SF-GNPs showed absence of systemic toxicological effects including hematological, biochemical and histological parameters. More importantly, the histopathological analysis of vital organs such as liver, brain, lung, kidney and heart showed very least or no sign of inflammation, cell infiltration, necrosis, tissue disorganization or fibrotic reactions after intra-peritoneal administration of SF-GNP nanoconjugates in animals. However, SF-GNP nanoconjugates significantly reduced (>80%) the percentage cell survival and the size and number of SF resistant solid tumor colonies of HepG2 cells in 3D model system. The exposure of SF-GNP nanoconjugate to SF resistant HepG2 cell colonies also provided evidence for anti-proliferative effect and reversal of drug resistance by elucidating the molecular regulatory mechanisms of extracellular matrix factor (CD147), tumor growth factor (TGF-β), hepatoma upregulated protein (hURP) and drug transporter (ABCG-2).Sandeep Kumar VishwakarmaPriyanka SharmilaAvinash BardiaLakkireddy ChandrakalaN. RajuG. SravaniB. V. S. SastryMd Aejaz HabeebAleem Ahmed KhanMarshal DhayalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Sandeep Kumar Vishwakarma
Priyanka Sharmila
Avinash Bardia
Lakkireddy Chandrakala
N. Raju
G. Sravani
B. V. S. Sastry
Md Aejaz Habeeb
Aleem Ahmed Khan
Marshal Dhayal
Use of Biocompatible Sorafenib-gold Nanoconjugates for Reversal of Drug Resistance in Human Hepatoblatoma Cells
description Abstract The present study identifies the potential of highly biocompatible SF-GNP nano-conjugate to enhance the chemotherapeutic response to combat drug resistance in cancer cells. We developed a stable colloidal suspension of sorafenib-gold nanoconjugate (SF-GNP) of <10 nm size in aqueous medium for reverting the cancer drug resistance in SF-resistant HepG2 cells in a 3D ex-vivo model system. In-vivo biocompatibility assay of SF-GNPs showed absence of systemic toxicological effects including hematological, biochemical and histological parameters. More importantly, the histopathological analysis of vital organs such as liver, brain, lung, kidney and heart showed very least or no sign of inflammation, cell infiltration, necrosis, tissue disorganization or fibrotic reactions after intra-peritoneal administration of SF-GNP nanoconjugates in animals. However, SF-GNP nanoconjugates significantly reduced (>80%) the percentage cell survival and the size and number of SF resistant solid tumor colonies of HepG2 cells in 3D model system. The exposure of SF-GNP nanoconjugate to SF resistant HepG2 cell colonies also provided evidence for anti-proliferative effect and reversal of drug resistance by elucidating the molecular regulatory mechanisms of extracellular matrix factor (CD147), tumor growth factor (TGF-β), hepatoma upregulated protein (hURP) and drug transporter (ABCG-2).
format article
author Sandeep Kumar Vishwakarma
Priyanka Sharmila
Avinash Bardia
Lakkireddy Chandrakala
N. Raju
G. Sravani
B. V. S. Sastry
Md Aejaz Habeeb
Aleem Ahmed Khan
Marshal Dhayal
author_facet Sandeep Kumar Vishwakarma
Priyanka Sharmila
Avinash Bardia
Lakkireddy Chandrakala
N. Raju
G. Sravani
B. V. S. Sastry
Md Aejaz Habeeb
Aleem Ahmed Khan
Marshal Dhayal
author_sort Sandeep Kumar Vishwakarma
title Use of Biocompatible Sorafenib-gold Nanoconjugates for Reversal of Drug Resistance in Human Hepatoblatoma Cells
title_short Use of Biocompatible Sorafenib-gold Nanoconjugates for Reversal of Drug Resistance in Human Hepatoblatoma Cells
title_full Use of Biocompatible Sorafenib-gold Nanoconjugates for Reversal of Drug Resistance in Human Hepatoblatoma Cells
title_fullStr Use of Biocompatible Sorafenib-gold Nanoconjugates for Reversal of Drug Resistance in Human Hepatoblatoma Cells
title_full_unstemmed Use of Biocompatible Sorafenib-gold Nanoconjugates for Reversal of Drug Resistance in Human Hepatoblatoma Cells
title_sort use of biocompatible sorafenib-gold nanoconjugates for reversal of drug resistance in human hepatoblatoma cells
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/d0e4b84a554d47299fdab6cb2a459a2a
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