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Issue 35, 2013
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Glutathione-sensitive nanoplatform for monitored intracellular delivery and controlled release of Camptothecin

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Abstract

We report the design, synthesis, characterization and in vitro testing of a novel nanodrug based on a covalent linking model that allows intracellular controlled release of the pharmaceutical payload. A new synthetic strategy is implemented by direct coupling of as-synthesized (pyridin-2-yldisulfanyl)alkyl carbonate derivatives of camptothecin (CPT) with thiol groups of silica hybrid nanoparticles containing a non-porous core and a mesoporous shell. Upon reaction with thiols in physiological conditions, disulfide bridge cleavage occurs, releasing the naked drug after an intramolecular cyclization mechanism. Additional incorporation of a fluorophore into particles core facilitates imaging at the subcellular level for the monitoring of uptake and delivery. Confocal microscopy experiments in HeLa cervix cancer cells confirms that nanoparticles enter the cells by endocytosis but are able to escape from endo-lysosomes and enter the cytosolic compartment to release their cargo. The incorporation to cells of L-buthionine-sulfoximine, a glutathione inhibitor allows concluding that the intracellular releasing mechanism is mainly driven by the reducing activity of this tripeptide. This camptothecin nanoplatform shows the same cytotoxic activity than the free drug and is clearly superior to those release systems depending on enzymatic hydrolysis (as determined by calculation of the IC50 ratios).

Graphical abstract: Glutathione-sensitive nanoplatform for monitored intracellular delivery and controlled release of Camptothecin

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Publication details

The article was received on 21 Mar 2013, accepted on 11 Jun 2013 and first published on 13 Jun 2013


Article type: Paper
DOI: 10.1039/C3RA41404C
Citation: RSC Adv., 2013,3, 15121-15131
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    Glutathione-sensitive nanoplatform for monitored intracellular delivery and controlled release of Camptothecin

    C. Muniesa, V. Vicente, M. Quesada, S. Sáez-Atiénzar, J. R. Blesa, I. Abasolo, Y. Fernández and P. Botella, RSC Adv., 2013, 3, 15121
    DOI: 10.1039/C3RA41404C

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