Факультет хімії та фармації

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https://dspace.onu.edu.ua/handle/123456789/13483

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Перегляд Факультет хімії та фармації за Автор "Бондар, Катерина Вікторівна"

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    Документ
    Барвники зі змінною флуоресценцією для моніторингу адресної доставки ліків
    (Одеський національний університет імені І. І. Мечникова, 2018) Бондар, Катерина Вікторівна; Bondar, Kateryna
    Targeted drug delivery (TDD) including monitoring of drug release improves the quality of anti-cancer treatment. A basic drug delivery system (conjugate) consists of a turn-on switchable fluorescent reporter bound to a drug and to a targeting carrier that increases selectivity of drug delivery to the treated cells or tissue. When drug is released, the fluorescence intensity increases signaling the drug delivery event. At the moment there is a pronounced lack of fluorescent dyes suitable as the switchable reporters for TDD while the exciting switchable reporters have certain shortcomings such as poor dynamic range of the fluorescence intensity increase upon the drug release, insufficient brightness within the long-wavelength spectral region, and/or an increased toxicity. These drawbacks decrease efficiency of anti-cancer treatment. In this work, we synthesize novel, switchable TDD reporters based on the styryl and oxonol dyes, investigate spectral properties of these new dyes, and evaluate these reporters and their conjugates with a drug simulating compound. In particular, we develop synthetic approaches for the new, indolenine based, hydrophilic 4-hydroxy-styryl- and (4-hydroxyphenyl)buta-1,3-dienyl styryl dyes and pentamethine oxonol dye containing terminal 1,3-diphenyl-1H-pyrazol-5(4H)-one terminal moieties and synthesize these dyes using the developed approaches. Hydroxylic function of the obtained styryl dyes is derivatized by acetyl group that simulate a potential drug moiety. Spectral properties of the dyes and the acetyl group cleavage profiles are investigated and it is evidenced that these dyes have a great potential as the basic structures for further the development of switchable reporters for TDD monitoring. The obtained results are promising and indicate that further research in the field of styryl and oxonol based switchable reporters may help to succeed in the development of efficient fluorescence based systems for targeted drug delivery.