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Slow-targeted release of a ruthenium anticancer agent from vitamin B12 functionalized marine diatom microalgae

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Abstract

Herein we report the synthesis of a new biomaterial designed for targeted delivery of poorly water-soluble inorganic anticancer drugs, with a focus on colorectal cancer. Diatomaceous earth microparticles derived from marine microalgae were coated with vitamin B12 (cyanocobalamin) as a tumor targeting agent and loaded with the well-known anticancer agents cisplatin, 5-fluorouracil (5-FU), and a tris-tetraethyl[2,2′-bipyridine]-4,4′-diamine–ruthenium(II) complex. The successful functionalization of the biomaterial was demonstrated by different analytical techniques and by synthesizing an organometallic fluorescein analogue of cyanocobalamin detectable by confocal laser scanning microscopy. The drug releasing properties were evaluated for all three species. We found that while cisplatin and 5-FU are rapidly lost from the material, the ruthenium complex showed an unprecedented release profile, being retained in the material up to 5 days in aqueous media but readily released in lipophilic environments as in the cell membrane. The increased adherence of the B12 coated diatoms to colorectal cancer cell line HT-29 and breast cancer cell line MCF-7 was demonstrated in vitro. In both cases, the adherence of the B12 modified diatoms was at least 3 times higher than that of the unmodified ones and was correlated with the increased transcobalamin II (TC(II)) and transcobalamin II receptor (TC(II)-R) expression of the targeted tissue. Our results suggest that this type of B12 modified diatoms could be a promising tool to achieve targeted delivery of water insoluble inorganic complexes to tumor tissues by acting as a micro-shuttle interacting with the sites of interest before delivering the drug in the vicinity of the tumor tissue.

Graphical abstract: Slow-targeted release of a ruthenium anticancer agent from vitamin B12 functionalized marine diatom microalgae

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Publication details

The article was received on 17 Jul 2018, accepted on 18 Sep 2018 and first published on 19 Sep 2018


Article type: Paper
DOI: 10.1039/C8DT02914H
Citation: Dalton Trans., 2018, Advance Article
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    Slow-targeted release of a ruthenium anticancer agent from vitamin B12 functionalized marine diatom microalgae

    J. Delasoie, J. Rossier, L. Haeni, B. Rothen-Rutishauser and F. Zobi, Dalton Trans., 2018, Advance Article , DOI: 10.1039/C8DT02914H

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