Enhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most aggressive and commonly diagnosed brain cancer and is highly resistant to routine chemotherapeutic drugs. The present study involves the synthesis of Lignin-g-p (NIPAM-co-DMAEMA) gold nanogel, loaded with curcumin and piperine, to treat GBM. The ongoing stud...

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Autores principales:	Bilal Javed, Xinyi Zhao, Daxiang Cui, James Curtin, Furong Tian
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	caspase-3 apoptosis cancer drug delivery glioblastoma multiforme gold nanoparticles immunostaining Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3d9d01c441db40b0a7d8d1cf5ceac10c
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spelling	oai:doaj.org-article:3d9d01c441db40b0a7d8d1cf5ceac10c2021-11-25T16:48:27ZEnhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme10.3390/biomedicines91115162227-9059https://doaj.org/article/3d9d01c441db40b0a7d8d1cf5ceac10c2021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1516https://doaj.org/toc/2227-9059Glioblastoma multiforme (GBM) is the most aggressive and commonly diagnosed brain cancer and is highly resistant to routine chemotherapeutic drugs. The present study involves the synthesis of Lignin-g-p (NIPAM-co-DMAEMA) gold nanogel, loaded with curcumin and piperine, to treat GBM. The ongoing study has the application potential to (1) overcome the limitations of drugs biodistribution, (2) enhance the toxicity of anticancer drugs against GBM, and (3) identify the drugs uptake pathway. Atom transfer radical polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and morphological analysis confirmed that the drug-loaded gold nanogels are spherical and exist in the size of 180 nm. The single and combinatorial toxicity effects of curcumin- and piperine-loaded Lignin-g-p (NIPAM-co-DMAEMA) gold nanogels were studied against U-251 MG GBM cells. A cytotoxicity analysis displayed anticancer properties. IC<sub>50</sub> of curcumin- and piperine-loaded gold nanogels were recorded at 30 μM and 35 μM, respectively. Immunostaining and Western blot analysis confirmed the protein expression of caspase-3 and cleaved caspase-3 in cells treated with drug-loaded nanogels. Kinetic drug release revealed 86% release of hybrid curcumin–piperine from gold nanogel after 250 min at pH 4. Atomic absorption spectroscopic analysis confirmed that the drug-loaded nanogels have better internalization or association with the cancer cells than the GNPs or nano-gels alone. Morphological studies further confirmed that the curcumin and piperine nanogels penetrate the cells via endocytic pathways and induce caspase-3-related apoptosis. The experimental evidence shows the enhanced properties of combinatorial curcumin–piperine gold nanogels (IC50: 21 μM) to overcome the limitations of conventional chemotherapeutic treatments of glioma cells.Bilal JavedXinyi ZhaoDaxiang CuiJames CurtinFurong TianMDPI AGarticlecaspase-3 apoptosiscancerdrug deliveryglioblastoma multiformegold nanoparticlesimmunostainingBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1516, p 1516 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	caspase-3 apoptosis cancer drug delivery glioblastoma multiforme gold nanoparticles immunostaining Biology (General) QH301-705.5
spellingShingle	caspase-3 apoptosis cancer drug delivery glioblastoma multiforme gold nanoparticles immunostaining Biology (General) QH301-705.5 Bilal Javed Xinyi Zhao Daxiang Cui James Curtin Furong Tian Enhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme
description	Glioblastoma multiforme (GBM) is the most aggressive and commonly diagnosed brain cancer and is highly resistant to routine chemotherapeutic drugs. The present study involves the synthesis of Lignin-g-p (NIPAM-co-DMAEMA) gold nanogel, loaded with curcumin and piperine, to treat GBM. The ongoing study has the application potential to (1) overcome the limitations of drugs biodistribution, (2) enhance the toxicity of anticancer drugs against GBM, and (3) identify the drugs uptake pathway. Atom transfer radical polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and morphological analysis confirmed that the drug-loaded gold nanogels are spherical and exist in the size of 180 nm. The single and combinatorial toxicity effects of curcumin- and piperine-loaded Lignin-g-p (NIPAM-co-DMAEMA) gold nanogels were studied against U-251 MG GBM cells. A cytotoxicity analysis displayed anticancer properties. IC<sub>50</sub> of curcumin- and piperine-loaded gold nanogels were recorded at 30 μM and 35 μM, respectively. Immunostaining and Western blot analysis confirmed the protein expression of caspase-3 and cleaved caspase-3 in cells treated with drug-loaded nanogels. Kinetic drug release revealed 86% release of hybrid curcumin–piperine from gold nanogel after 250 min at pH 4. Atomic absorption spectroscopic analysis confirmed that the drug-loaded nanogels have better internalization or association with the cancer cells than the GNPs or nano-gels alone. Morphological studies further confirmed that the curcumin and piperine nanogels penetrate the cells via endocytic pathways and induce caspase-3-related apoptosis. The experimental evidence shows the enhanced properties of combinatorial curcumin–piperine gold nanogels (IC50: 21 μM) to overcome the limitations of conventional chemotherapeutic treatments of glioma cells.
format	article
author	Bilal Javed Xinyi Zhao Daxiang Cui James Curtin Furong Tian
author_facet	Bilal Javed Xinyi Zhao Daxiang Cui James Curtin Furong Tian
author_sort	Bilal Javed
title	Enhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme
title_short	Enhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme
title_full	Enhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme
title_fullStr	Enhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme
title_full_unstemmed	Enhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme
title_sort	enhanced anticancer response of curcumin- and piperine-loaded lignin-g-p (nipam-co-dmaema) gold nanogels against u-251 mg glioblastoma multiforme
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3d9d01c441db40b0a7d8d1cf5ceac10c
work_keys_str_mv	AT bilaljaved enhancedanticancerresponseofcurcuminandpiperineloadedligningpnipamcodmaemagoldnanogelsagainstu251mgglioblastomamultiforme AT xinyizhao enhancedanticancerresponseofcurcuminandpiperineloadedligningpnipamcodmaemagoldnanogelsagainstu251mgglioblastomamultiforme AT daxiangcui enhancedanticancerresponseofcurcuminandpiperineloadedligningpnipamcodmaemagoldnanogelsagainstu251mgglioblastomamultiforme AT jamescurtin enhancedanticancerresponseofcurcuminandpiperineloadedligningpnipamcodmaemagoldnanogelsagainstu251mgglioblastomamultiforme AT furongtian enhancedanticancerresponseofcurcuminandpiperineloadedligningpnipamcodmaemagoldnanogelsagainstu251mgglioblastomamultiforme
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Enhanced Anticancer Response of Curcumin- and Piperine-Loaded Lignin-g-p (NIPAM-co-DMAEMA) Gold Nanogels against U-251 MG Glioblastoma Multiforme

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