Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer

Sneha Mahalunkar,1 Amit Singh Yadav,2 Mahadeo Gorain,2 Vinay Pawar,3,4 Ranveig Braathen,5,6 Siegfried Weiss,3 Bjarne Bogen,5,6 Suresh W Gosavi,7 Gopal C Kundu2 1School of Basic Medical Science, Savitribai Phule Pune University, Pune 411007, Maharashtra, India; 2Laboratory of Tumor Biology, Angiogene...

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Autores principales:	Mahalunkar S, Yadav AS, Gorain M, Pawar V, Braathen R, Weiss S, Bogen B, Gosavi SW, Kundu GC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Curcumin gold nanoconjugate folic acid breast cancer cell line cytotoxic activity. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4a314e8013894ebeaf96240e15b1c046
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id	oai:doaj.org-article:4a314e8013894ebeaf96240e15b1c046
record_format	dspace
institution	DOAJ
collection	DOAJ
language	EN
topic	Curcumin gold nanoconjugate folic acid breast cancer cell line cytotoxic activity. Medicine (General) R5-920
spellingShingle	Curcumin gold nanoconjugate folic acid breast cancer cell line cytotoxic activity. Medicine (General) R5-920 Mahalunkar S Yadav AS Gorain M Pawar V Braathen R Weiss S Bogen B Gosavi SW Kundu GC Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer
description	Sneha Mahalunkar,1 Amit Singh Yadav,2 Mahadeo Gorain,2 Vinay Pawar,3,4 Ranveig Braathen,5,6 Siegfried Weiss,3 Bjarne Bogen,5,6 Suresh W Gosavi,7 Gopal C Kundu2 1School of Basic Medical Science, Savitribai Phule Pune University, Pune 411007, Maharashtra, India; 2Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS), Pune 411007, India; 3Institute of Immunology, Hannover Medical School, Hannover, Germany; 4Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany; 5K.G. Jebsen Centre for Influenza Vaccines Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 6Oslo University Hospital, Oslo 0027, Norway; 7Department of Physics, Savitribai Phule Pune University, Pune 411007, Maharashtra, IndiaCorrespondence: Gopal C KunduLaboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS), Pune 411007, IndiaTel +91 202 570 8104Fax +91 202 569 2259Email kundu@nccs.res.in Suresh W GosaviDepartment of Physics, Savitribai Phule Pune University, Pune 411007, Maharashtra, IndiaTel +91 202 569 2678Fax +91 202 569 1684Email swg@physics.unipune.ac.inBackground: Curcumin has been widely used owing to its various medicinal properties including antitumor effects. However, its clinical application is limited by its instability, poor solubility and low bioavailability. Folic acid (FA)-functionalized nanoformulations may enhance the sustained release of an anticancer drug (curcumin) by tumor-specific targeting to improve therapeutic benefit. This study aims to design a nanoconjugate (NC) comprised of folate–curcumin-loaded gold–polyvinylpyrrolidone nanoparticles (FA–CurAu-PVP NPs) for targeted delivery in breast cancer model systems.Methods: We developed curcumin-loaded FA-functionalized Au-PVP NCs by layer-by-layer assembly. The folic acid–curcumin Au-PVP NCs (FA–CurAu-PVP NCs) were characterized by ultraviolet–visible spectra, Fourier transform infrared spectroscopy, X-ray powder diffraction and thermogravimetric analysis. In vitro anticancer and antimigratory effects of NCs were examined by performing MTT and wound migration assays. The in vivo antitumor efficacy of NCs was investigated using a preclinical breast cancer orthotopic mouse model.Results: Curcumin (40 μg/mL) was loaded along with conjugation of folate onto Au-PVP NPs to form FA–CurAu-PVP NCs. The size and charge of the NCs were increased gradually through layer-by-layer assembly and showed 80% release of curcumin at acidic pH. The NC did not show aggregation when incubated with human serum and mimicked an intrinsic peroxidase-like property in the presence of 3,3ʹ,5,5ʹ-tetramethylbenzidine substrate. The MTT data using these NCs showed efficient anticancer activity at lower doses in estrogen/progesterone receptor (ER/PR)-negative cells compared with ER/PR-positive cells. Furthermore, the NCs did not show cytotoxicity at the investigated concentration in human breast epithelial and mouse fibroblast cell lines. They showed inhibitory effects on cell migration and high antitumor efficacy in in vivo analysis.Conclusion: These results suggest that folate-based tumor targeting using CurAu-PVP NCs is a promising approach for tumor-specific therapy of breast cancer without harming normal cells.Keywords: curcumin, gold nanoconjugate, folic acid, breast cancer cell line, cytotoxic activity
format	article
author	Mahalunkar S Yadav AS Gorain M Pawar V Braathen R Weiss S Bogen B Gosavi SW Kundu GC
author_facet	Mahalunkar S Yadav AS Gorain M Pawar V Braathen R Weiss S Bogen B Gosavi SW Kundu GC
author_sort	Mahalunkar S
title	Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer
title_short	Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer
title_full	Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer
title_fullStr	Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer
title_full_unstemmed	Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer
title_sort	functional design of ph-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/4a314e8013894ebeaf96240e15b1c046
work_keys_str_mv	AT mahalunkars functionaldesignofphresponsivefolatetargetedpolymercoatedgoldnanoparticlesfordrugdeliveryandinvivotherapyinbreastcancer AT yadavas functionaldesignofphresponsivefolatetargetedpolymercoatedgoldnanoparticlesfordrugdeliveryandinvivotherapyinbreastcancer AT gorainm functionaldesignofphresponsivefolatetargetedpolymercoatedgoldnanoparticlesfordrugdeliveryandinvivotherapyinbreastcancer AT pawarv functionaldesignofphresponsivefolatetargetedpolymercoatedgoldnanoparticlesfordrugdeliveryandinvivotherapyinbreastcancer AT braathenr functionaldesignofphresponsivefolatetargetedpolymercoatedgoldnanoparticlesfordrugdeliveryandinvivotherapyinbreastcancer AT weisss functionaldesignofphresponsivefolatetargetedpolymercoatedgoldnanoparticlesfordrugdeliveryandinvivotherapyinbreastcancer AT bogenb functionaldesignofphresponsivefolatetargetedpolymercoatedgoldnanoparticlesfordrugdeliveryandinvivotherapyinbreastcancer AT gosavisw functionaldesignofphresponsivefolatetargetedpolymercoatedgoldnanoparticlesfordrugdeliveryandinvivotherapyinbreastcancer AT kundugc functionaldesignofphresponsivefolatetargetedpolymercoatedgoldnanoparticlesfordrugdeliveryandinvivotherapyinbreastcancer
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spelling	oai:doaj.org-article:4a314e8013894ebeaf96240e15b1c0462021-12-02T10:42:59ZFunctional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer1178-2013https://doaj.org/article/4a314e8013894ebeaf96240e15b1c0462019-10-01T00:00:00Zhttps://www.dovepress.com/functional-design-of-ph-responsive-folate-targeted-polymer-coated-gold-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sneha Mahalunkar,1 Amit Singh Yadav,2 Mahadeo Gorain,2 Vinay Pawar,3,4 Ranveig Braathen,5,6 Siegfried Weiss,3 Bjarne Bogen,5,6 Suresh W Gosavi,7 Gopal C Kundu2 1School of Basic Medical Science, Savitribai Phule Pune University, Pune 411007, Maharashtra, India; 2Laboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS), Pune 411007, India; 3Institute of Immunology, Hannover Medical School, Hannover, Germany; 4Department of Molecular Bacteriology, Helmholtz Centre for Infection Research, Braunschweig, Germany; 5K.G. Jebsen Centre for Influenza Vaccines Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 6Oslo University Hospital, Oslo 0027, Norway; 7Department of Physics, Savitribai Phule Pune University, Pune 411007, Maharashtra, IndiaCorrespondence: Gopal C KunduLaboratory of Tumor Biology, Angiogenesis and Nanomedicine Research, National Centre for Cell Science (NCCS), Pune 411007, IndiaTel +91 202 570 8104Fax +91 202 569 2259Email kundu@nccs.res.in Suresh W GosaviDepartment of Physics, Savitribai Phule Pune University, Pune 411007, Maharashtra, IndiaTel +91 202 569 2678Fax +91 202 569 1684Email swg@physics.unipune.ac.inBackground: Curcumin has been widely used owing to its various medicinal properties including antitumor effects. However, its clinical application is limited by its instability, poor solubility and low bioavailability. Folic acid (FA)-functionalized nanoformulations may enhance the sustained release of an anticancer drug (curcumin) by tumor-specific targeting to improve therapeutic benefit. This study aims to design a nanoconjugate (NC) comprised of folate–curcumin-loaded gold–polyvinylpyrrolidone nanoparticles (FA–CurAu-PVP NPs) for targeted delivery in breast cancer model systems.Methods: We developed curcumin-loaded FA-functionalized Au-PVP NCs by layer-by-layer assembly. The folic acid–curcumin Au-PVP NCs (FA–CurAu-PVP NCs) were characterized by ultraviolet–visible spectra, Fourier transform infrared spectroscopy, X-ray powder diffraction and thermogravimetric analysis. In vitro anticancer and antimigratory effects of NCs were examined by performing MTT and wound migration assays. The in vivo antitumor efficacy of NCs was investigated using a preclinical breast cancer orthotopic mouse model.Results: Curcumin (40 μg/mL) was loaded along with conjugation of folate onto Au-PVP NPs to form FA–CurAu-PVP NCs. The size and charge of the NCs were increased gradually through layer-by-layer assembly and showed 80% release of curcumin at acidic pH. The NC did not show aggregation when incubated with human serum and mimicked an intrinsic peroxidase-like property in the presence of 3,3ʹ,5,5ʹ-tetramethylbenzidine substrate. The MTT data using these NCs showed efficient anticancer activity at lower doses in estrogen/progesterone receptor (ER/PR)-negative cells compared with ER/PR-positive cells. Furthermore, the NCs did not show cytotoxicity at the investigated concentration in human breast epithelial and mouse fibroblast cell lines. They showed inhibitory effects on cell migration and high antitumor efficacy in in vivo analysis.Conclusion: These results suggest that folate-based tumor targeting using CurAu-PVP NCs is a promising approach for tumor-specific therapy of breast cancer without harming normal cells.Keywords: curcumin, gold nanoconjugate, folic acid, breast cancer cell line, cytotoxic activityMahalunkar SYadav ASGorain MPawar VBraathen RWeiss SBogen BGosavi SWKundu GCDove Medical PressarticleCurcumingold nanoconjugatefolic acidbreast cancer cell linecytotoxic activity.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 8285-8302 (2019)

Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer

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