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 Publisher Pubmed



Ghorbani M¹ ; Bigdeli B² ; Jalilibaleh L³ ; Baharifar H⁴ ; Akrami M⁶ ; Dehghani S⁵ ; Goliaei B² ; Amani A⁴ ; Lotfabadi A⁶ ; Rashedi H¹ ; Haririan I⁶ ; Alam NR⁵ ; Hamedani MP⁷ ; Khoobi M^{3, 6}
Source: European Journal of Pharmaceutical Sciences Published:2018

Abstract

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. © 2017 Elsevier B.V.