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dc.creatorIgnjatović, Nenad
dc.creatorSakač, Marija
dc.creatorKuzminac, Ivana
dc.creatorKojić, Vesna V.
dc.creatorMarković, Smilja B.
dc.creatorVasiljević-Radović, Dana
dc.creatorWu, Victoria
dc.creatorUskoković, Vuk
dc.creatorUskoković, Dragan
dc.date.accessioned2019-10-15T13:48:01Z
dc.date.available2019-10-09
dc.date.available2019-10-15T13:48:01Z
dc.date.issued2018
dc.identifier.issn2050-750X
dc.identifier.issn2050-7518
dc.identifier.urihttp://dais.sanu.ac.rs/123456789/4066
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/3146
dc.description.abstractLow 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: d50 = 138 nm for A-loaded HAp/ChOSL and d50 = 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.sr
dc.language.isoensr
dc.publisherRoyal Society of Chemistrysr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/45004/RS//sr
dc.relationUnited States National Institutes of Health (NIH) / National Institute of Dental and Craniofacial Research (NIDCR), Grant K99-DE021416sr
dc.rightsembargoedAccesssr
dc.sourceJournal of Materials Chemistry Bsr
dc.subjectchitosan oligosaccharide lactatesr
dc.subjecthydroxyapatitesr
dc.subjectnanoparticlessr
dc.subjectdrug deliverysr
dc.subjectcancer cell targetingsr
dc.titleChitosan oligosaccharide lactate coated hydroxyapatite nanoparticles as a vehicle for the delivery of steroid drugs and the targeting of breast cancer cellssr
dc.typearticlesr
dc.rights.licenseBY-NC-NDsr
dcterms.abstractВасиљевић-Радовић, Дана; Којић, Весна; Кузминац, Ивана; Ускоковић, Вук; Сакач, Марија; Игњатовић, Ненад; Wу, Вицториа; Ускоковић, Драган; Марковић, Смиља;
dc.citation.volume6
dc.citation.spage6957
dc.citation.epage6968
dc.citation.rankM21
dc.description.otherThis is the peer-reviewed version of the article: Ignjatović, Nenad L., Marija Sakač, Ivana Kuzminac, Vesna Kojić, Smilja Marković, Dana Vasiljević-Radović, Victoria M. Wu, Vuk Uskoković, and Dragan P. Uskoković. 2018. “Chitosan Oligosaccharide Lactate Coated Hydroxyapatite Nanoparticles as a Vehicle for the Delivery of Steroid Drugs and the Targeting of Breast Cancer Cells.” Journal of Materials Chemistry B, [https://doi.org/10.1039/C8TB01995A]sr
dc.description.other[http://cer.ihtm.bg.ac.rs/handle/123456789/2482]
dc.identifier.doi10.1039/C8TB01995A
dc.identifier.fulltexthttp://cer.ihtm.bg.ac.rs/bitstream/id/14203/Ignjatovic_RSC-2018.pdf
dc.identifier.scopus2-s2.0-85056324409
dc.identifier.wos000449701500007
dc.type.versionacceptedVersionsr


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