Chitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cells 机翻标题: 暂无翻译,请尝试点击翻译按钮。

来源
Journal of Materials Chemistry, B. materials for biology and medicine
年/卷/期
2018 / 6 / 43
页码
6957-6968
ISSN号
2050-750X
作者单位
Chapman Univ, Ctr Targeted Drug Delivery, Dept Biomed & Pharmaceut Sci, Adv Mat & Nanobiotechnol Lab, 9501 Jeronimo Rd, Irvine, CA 92618 USA;Univ Novi Sad, Fac Sci, Dept Chem Biochem & Environm Protect, Trg Dositeja Obradovica 3, Novi Sad 21000, Serbia;Univ Novi Sad, Fac Sci, Dept Chem Biochem & Environm Protect, Trg Dositeja Obradovica 3, Novi Sad 21000, Serbia;Univ Novi Sad, Oncol Inst Vojvodina, Fac Med, Put Dr Goldmana 4, Sremska Kamenica 21204, Serbia;Serbian Acad Arts & Sci, Inst Tech Sci, Knez Mihailova 35-4,POB 377, Belgrade 11000, Serbia;Univ Belgrade, Inst Chem Technol & Met, Njegoseva 12, Belgrade, Serbia;Serbian Acad Arts & Sci, Inst Tech Sci, Knez Mihailova 35-4,POB 377, Belgrade 11000, Serbia;Univ Illinois, Dept Bioengn, Adv Mat & Nanobiotechnol Lab, Chicago, IL USA;Serbian Acad Arts & Sci, Inst Tech Sci, Knez Mihailova 35-4,POB 377, Belgrade 11000, Serbia;
作者
Wu, Victoria M.;Sakac, Marija;Kuzminac, Ivana;Kojic, Vesna;Markovic, Smilja;Vasiljevic-Radovic, Dana;Ignjatovic, Nenad L.;Uskokovic, Vuk;Uskokovic, Dragan P.;
摘要
Low targeting efficiency and fast metabolism of antineoplastic drugs are hindrances to effective chemotherapies and there is an ongoing search for better drugs, but also better carriers. Steroid derivatives, 3-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3,17-dihydroxy-16-hydroxymino-androst-5-ene (B) as cancer growth inhibitors were chemically synthesized and captured in a carrier composed of hydroxyapatite (HAp) nanoparticles coated with chitosan oligosaccharide lactate (ChOLS). The only difference between the two derivatives is that A has a carbonyl group at the C17 position of the five-membered ring and B has a hydroxyl. This small difference in the structure resulted not only in different physicochemical properties of the A- and B-loaded HAp/ChOSL, but also in different biological activities. The morphology of drug-loaded HAp/ChOSL particles was spherical, but the size depended on the drug identity: d(50) = 138 nm for A-loaded HAp/ChOSL and d(50) = 223 nm for B-loaded HAp/ChOSL. Cell-selective toxicity was tested against human breast carcinoma (MCF7 and MDA-MB-231), human lung carcinoma (A549) and human lung fibroblasts (MRC-5). The small selectivity of pure derivatives A and B toward breast cancer cells became drastically increased when they were delivered using HAp/ChOSL particles. Whereas the ratio of the cytotoxicity imposed onto breast cancer cells and the cytotoxicity imposed onto healthy MRC-5 fibroblasts ranged from 1.5 to 1.7 for pure A and from 1.5 to 2.3 for pure derivative B depending on the concentration, it increased to 5.4 for A-loaded HAp/ChOSL and 5.1 for B-loaded HAp/ChOSL. FACS analysis demonstrated poor uptake of HAp/ChOSL particles by MCF7 cells, suggesting that the drug release occurs extracellularly. The augmented activity of the drugs was most likely due to sustained release, although the favorable positive charge of the carrier, allowing it to adhere to the negatively charged plasma membrane and release the drugs steadily and directly to the hydrophobic cell membrane milieu, was delineated as a possible complementary mechanism.
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