title: Supramolecular formulation of nitidine chloride can alleviate its hepatotoxicity and improve its anticancer activity.
abstract: Nitidine chloride (NC) has demonstrated promising anticancer activity. However, NC has also shown non-specific toxicity in various healthy organs such as the liver. In this study, we aimed to develop a supramolecular formulation of NC and investigate the associated benefits of such a supramolecular formulation on modulating its inherent hepatotoxicity and anticancer activity. The formation of NC-cucurbit[7]uil (NC@CB[7]) complexes was characterized by1H nuclear magnetic resonance and Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffraction analysis. As a consequence of the supramolecular complexation, NC@CB[7] showed significantly lower toxicity (IC50: 6.87 ± 0.80 μM) on a liver cell line (LO2), and higher cytotoxicity (IC50: 2.94 ± 0.15 μM) on a breast cancer cell line (MCF-7), when compared with the free drug (IC50of 3.48 ± 0.49 μM and 7.28 ± 0.36 μM, on these two cell lines, respectively). Investigation of cellular uptakes revealed that CB[7]'s capability in modulating the toxicity/activity of NC was mainly attributed to the drug's different cellular uptake behaviors that were influenced by CB[7]'s complexation. Taken together, we have demonstrated that supramolecular formulation of NC by CB[7] significantly alleviated its hepatotoxicity and improved its anticancer activity in vitro.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
authors.forename: Wanying
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yin
authors.affiliation: Aix Marseille Univ, CNRS, ICR, Marseille, France.
authors.forename: David
authors.initials: D
authors.lastname: Bardelang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. Electronic address: yzheng@umac.mo.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. Electronic address: rwang@umac.mo.
authors.forename: Ruibing
authors.initials: R
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity*; D053119:Benzophenanthridines / Q000737:chemistry* / Q000633:toxicity*; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004339:Drug Compounding; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000633:toxicity*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008099:Liver / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017550:Spectroscopy, Fourier Transform Infrared; D032106:Zanthoxylum / Q000737:chemistry*; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
chemical_list: D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D001952:Bridged-Ring Compounds; D004365:Drugs, Chinese Herbal; D007093:Imidazoles; C456276:cucurbit(7)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils; C013615:nitidine
keywords: Anticancer activity; Hepatotoxicity; Nitidine chloride; Supramolecular formulation; cucurbit[7]uril