Curcumin-lipoic acid conjugate as a promising anticancer agent on the surface of gold‑iron oxide nanocomposites: A pH-sensitive targeted drug delivery system for brain cancer theranostics

Ghorbani, M; Bigdeli, B; Jalili-baleh, L; Baharifar, H; Akrami, M; Dehghani, S; Goliaei, B; Amani, A; Lotfabadi, A; Rashedi, H; Haririan, I; Alam, NR; Hamedani, MP; Khoobi, M

Curcumin-lipoic acid conjugate as a promising anticancer agent on the surface of gold‑iron oxide nanocomposites: A pH-sensitive targeted drug delivery system for brain cancer theranostics

Ghorbani, M Bigdeli, B

Jalili-baleh, L Baharifar, H Akrami, M Dehghani, S Goliaei, B Amani, A Lotfabadi, A Rashedi, H Haririan, I Alam, NR Hamedani, MP Khoobi, M

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Publication Type:: Journal Article
Citation:: European Journal of Pharmaceutical Sciences, 2018, 114 pp. 175 - 188
Issue Date:: 2018-03-01

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Field	Value	Language
dc.contributor.author	Ghorbani, M	en_US
dc.contributor.author	Bigdeli, B https://orcid.org/0000-0002-6600-8983	en_US
dc.contributor.author	Jalili-baleh, L	en_US
dc.contributor.author	Baharifar, H	en_US
dc.contributor.author	Akrami, M	en_US
dc.contributor.author	Dehghani, S	en_US
dc.contributor.author	Goliaei, B	en_US
dc.contributor.author	Amani, A	en_US
dc.contributor.author	Lotfabadi, A	en_US
dc.contributor.author	Rashedi, H	en_US
dc.contributor.author	Haririan, I	en_US
dc.contributor.author	Alam, NR	en_US
dc.contributor.author	Hamedani, MP	en_US
dc.contributor.author	Khoobi, M	en_US
dc.date.available	2017-12-09	en_US
dc.date.issued	2018-03-01	en_US
dc.identifier.citation	European Journal of Pharmaceutical Sciences, 2018, 114 pp. 175 - 188	en_US
dc.identifier.issn	0928-0987	en_US
dc.identifier.uri	http://hdl.handle.net/10453/132655
dc.description.abstract	© 2017 Elsevier B.V. Brain tumor is a lethal, fast growing cancer and a difficult case for treatment. Receptor-mediated endocytosis has been recognized as one of the most effective methods for drug delivery to brain tissue by overcoming obstacles associated with conventional therapeutics. In this work, a targeted theranostic drug delivery system (DDS) was prepared based on gold‑iron oxide nanocomposites (Fe3O4@Au NCs). Lipoic acid-curcumin (LA-CUR) was synthesized and introduced as a novel anticancer drug, and glutathione (GSH) was exploited as the targeting ligand. Both LA-CUR and GSH were easily attached to Fe3O4@Au NCs via Au-S interaction. As a negatively charged nanocarrier, the prepared DDS showed relatively less protein adsorption. Accordingly, hemocompatibility assays (complement, platelet, and leucocyte activation) revealed its hemocompatible virtue, especially in respect of free LA-CUR. GSH functionalization led to 2-fold increase of cellular uptake in GSH receptor-positive astrocyte cells which could primarily indicate the probable ability of the DDS to bypass BBB. Cytotoxicity and apoptosis assays together showed the noticeably enhanced cytotoxicity of LA-CUR against cancerous U87MG cells (IC50 = 2.69 μg/ml) in comparison with curcumin (IC50 = 21.31 μg/ml); moreover, the DDS demonstrated relatively higher cytotoxicity against cancerous U87MG cells than normal astrocyte cells which was in accordance with pH sensitive mechanism of LA-CUR release. Besides, the results of in vitro magnetic resonance imaging (MRI) (relaxation rate (r2) = 80.73 (s− 1·mM− 1)) primarily revealed that the DDS can be applied as a negative MRI contrast agent. In sum, the prepared DDS appeared to be a promising candidate for brain cancer treatment and a favorable MRI contrast agent.	en_US
dc.relation.ispartof	European Journal of Pharmaceutical Sciences	en_US
dc.relation.isbasedon	10.1016/j.ejps.2017.12.008	en_US
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.classification	Pharmacology & Pharmacy	en_US
dc.subject.mesh	Astrocytes	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Brain Neoplasms	en_US
dc.subject.mesh	Gold	en_US
dc.subject.mesh	Ferric Compounds	en_US
dc.subject.mesh	Curcumin	en_US
dc.subject.mesh	Thioctic Acid	en_US
dc.subject.mesh	Antineoplastic Agents	en_US
dc.subject.mesh	Drug Delivery Systems	en_US
dc.subject.mesh	X-Ray Diffraction	en_US
dc.subject.mesh	Hydrogen-Ion Concentration	en_US
dc.subject.mesh	Nanocomposites	en_US
dc.subject.mesh	Metal Nanoparticles	en_US
dc.subject.mesh	Theranostic Nanomedicine	en_US
dc.title	Curcumin-lipoic acid conjugate as a promising anticancer agent on the surface of gold‑iron oxide nanocomposites: A pH-sensitive targeted drug delivery system for brain cancer theranostics	en_US
dc.type	Journal Article
utslib.citation.volume	114	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	closed_access	*
pubs.publication-status	Published	en_US
pubs.volume	114	en_US

Abstract:

© 2017 Elsevier B.V. Brain tumor is a lethal, fast growing cancer and a difficult case for treatment. Receptor-mediated endocytosis has been recognized as one of the most effective methods for drug delivery to brain tissue by overcoming obstacles associated with conventional therapeutics. In this work, a targeted theranostic drug delivery system (DDS) was prepared based on gold‑iron oxide nanocomposites (Fe3O4@Au NCs). Lipoic acid-curcumin (LA-CUR) was synthesized and introduced as a novel anticancer drug, and glutathione (GSH) was exploited as the targeting ligand. Both LA-CUR and GSH were easily attached to Fe3O4@Au NCs via Au-S interaction. As a negatively charged nanocarrier, the prepared DDS showed relatively less protein adsorption. Accordingly, hemocompatibility assays (complement, platelet, and leucocyte activation) revealed its hemocompatible virtue, especially in respect of free LA-CUR. GSH functionalization led to 2-fold increase of cellular uptake in GSH receptor-positive astrocyte cells which could primarily indicate the probable ability of the DDS to bypass BBB. Cytotoxicity and apoptosis assays together showed the noticeably enhanced cytotoxicity of LA-CUR against cancerous U87MG cells (IC50 = 2.69 μg/ml) in comparison with curcumin (IC50 = 21.31 μg/ml); moreover, the DDS demonstrated relatively higher cytotoxicity against cancerous U87MG cells than normal astrocyte cells which was in accordance with pH sensitive mechanism of LA-CUR release. Besides, the results of in vitro magnetic resonance imaging (MRI) (relaxation rate (r2) = 80.73 (s− 1·mM− 1)) primarily revealed that the DDS can be applied as a negative MRI contrast agent. In sum, the prepared DDS appeared to be a promising candidate for brain cancer treatment and a favorable MRI contrast agent.

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http://hdl.handle.net/10453/132655