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Issue 25, 2012
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Cytotoxicity and slow release of the anti-cancer drugdoxorubicin from ZIF-8

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Abstract

Metal–organic frameworks are emerging as a powerful platform for the delivery and controlled release of several drug molecules. Herein, we report the incorporation of the anti-cancer drug doxorubicin into the zeolitic imidazolate framework (ZIF-8) with high-load and progressive release. Adsorption measurements show that doxorubicin is incorporated into ZIF-8 with a load of 0.049 g doxorubicin g−1 dehydrated ZIF-8. Doxorubicin is released in a highly controlled and progressive fashion with 66% of the drug released after 30 days. We also characterize the antitumoral potential and cytotoxicity of the doxorubicin-ZIF-8 (DOXO-ZIF-8) complex towards the mucoepidermoid carcinoma of human lung (NCI-H292), human colorectal adenocarcinoma (HT-29), and human promyelocytic leukemia (HL-60) cell lines. It is shown that the complex doxorubicin-ZIF-8 exhibits lower cytotoxicity than pure doxorubicin for the tested cells, possibly due to the slower release of the incorporated drug. Furthermore, host–guest interactions have been addressed from a microscopic perspective through molecular docking simulations. In conjunction with our experimental characterization, the calculations suggest that doxorubicin binds preferentially to the surface rather than into the pores of ZIF-8, whose entry diameter is at least half the size of the shortest axis of the drug. These findings are also consistent with high-resolution X-ray crystallography and NMR spectroscopy studies of ZIF-8 which shows that this framework is very rigid under constant pressure in contrast to previous experimental and theoretical studies of ZIF-8 under gas pressure.

Graphical abstract: Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8

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Supplementary files

Article information


Submitted
30 May 2012
Accepted
02 Aug 2012
First published
06 Aug 2012

RSC Adv., 2012,2, 9437-9442
Article type
Paper

Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8

I. B. Vasconcelos, T. G. D. Silva, G. C. G. Militão, T. A. Soares, N. M. Rodrigues, M. O. Rodrigues, N. B. D. Costa, R. O. Freire and S. A. Junior, RSC Adv., 2012, 2, 9437
DOI: 10.1039/C2RA21087H

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