Chitosan Oligosaccharide Lactate Coated Hydroxyapatite Nanoparticles as a Vehicle for the Delivery of Steroid Drugs and the Targeting of Breast Cancer Cells.

Autor: Ignjatović NL; Institute of Technical Sciences of the Serbian Academy of Science and Arts, Knez Mihailova 35/IV, P.O. Box 377, 11000 Belgrade, Serbia., Sakač M; University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia., Kuzminac I; University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia., Kojić V; Faculty of Medicine, Oncology Institute of Vojvodina, University of Novi Sad, Put Dr Goldmana 4, Sremska Kamenica 21204, Serbia., Marković S; Institute of Technical Sciences of the Serbian Academy of Science and Arts, Knez Mihailova 35/IV, P.O. Box 377, 11000 Belgrade, Serbia., Vasiljević-Radović D; University of Belgrade, Institute for Chemistry, Technology and Metallurgy, Njegoševa 12, Belgrade, Serbia., Wu VM; Advanced Materials and Nanobiotechnology Laboratory, Department of Biomedical and Pharmaceutical Sciences, Center for Targeted Drug Delivery, Chapman University, 9501 Jeronimo Road, Irvine, CA 92618, USA., Uskoković V; Advanced Materials and Nanobiotechnology Laboratory, Department of Bioengineering, University of Illinois, Chicago, IL, USA., Uskoković DP; Institute of Technical Sciences of the Serbian Academy of Science and Arts, Knez Mihailova 35/IV, P.O. Box 377, 11000 Belgrade, Serbia.
Jazyk: angličtina
Zdroj: Journal of materials chemistry. B [J Mater Chem B] 2018; Vol. 6 (43), pp. 6957-6968. Date of Electronic Publication: 2018 Oct 09.
DOI: 10.1039/C8TB01995A
Abstrakt: 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, 3β-hydroxy-16-hydroxymino-androst-5-en-17-one (A) and 3β,17β-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.
Competing Interests: Conflicts of interest There are no conflicts to declare.
Databáze: MEDLINE
Externí odkaz: