Аннотация
As the most abundant protein with a variety of physiological functions, albumin has been used extensively for the delivery of therapeutic molecules. Thiolactone chemistry provides a powerful tool to prepare spin-labeled albumin-based multimodal imaging probes and therapeutic agents. We report the synthesis of a tamoxifen homocysteine thiolactone derivative and its use in thiol-'click' chemistry to prepare multi-functionalized serum albumin. The released sulfhydryl group of the homocysteine functional handle was labeled with a nitroxide reagent to prepare a spin-labeled albumin-tamoxifen conjugate confirmed by MALDI-TOF-MS, EPR spectroscopy, UV-vis and fluorescent emission spectra. This is the basis for a novel multimodal tamoxifen-albumin theranostic with a significant (dose-dependent) inhibitory effect on the proliferation of malignant cells. The response of human glioblastoma multiforme T98G cells and breast cancer MCF-7 cells to tamoxifen and its albumin conjugates was different in tumor cells with different expression level of ERα in our experiments. These results provide further impetus to develop a serum protein for delivery of tamoxifen to cancer cells.
Язык оригинала | английский |
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Страницы (с-по) | 1314-1325 |
Число страниц | 12 |
Журнал | RSC Medicinal Chemistry |
Том | 11 |
Номер выпуска | 11 |
DOI | |
Состояние | Опубликовано - 2 апр. 2020 |
Предметные области OECD FOS+WOS
- 3.01.TU ФАРМАКОЛОГИЯ И ФАРМАЦИЯ
- 1.06.CQ БИОХИМИЯ И МОЛЕКУЛЯРНАЯ БИОЛОГИЯ