Mitochondrial targeting by use of lipid nanocapsules loaded with SV30, an analogue of the small-molecule Bcl-2 inhibitor HA14-1. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Journal of Controlled Release Année : 2011

Mitochondrial targeting by use of lipid nanocapsules loaded with SV30, an analogue of the small-molecule Bcl-2 inhibitor HA14-1.

M. Weyland
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F. Manero
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A. Paillard
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P. Menei
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P. Juin
J.-P. Benoit
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René Grée
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Emmanuel Garcion
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Résumé

Taking advantage from the development of SV30, a new analogue of the pro-apoptotic molecule HA14-1, the aim of this study was to functionally evaluate SV30 and to develop safe nanocarriers for its administration. By using an inversion phase process, 57nm organic solvent-free lipid nanocapsules loaded with SV30 (SV30-LNCs) were formulated. Biological performance of SV30 and SV30-LNCs were evaluated on F98 cells that express Bax and Bcl-2, through survival assays, HPLC, flow cytometry, confocal microscopy and spectral imaging. We observed that SV30 alone or in combination with paclitaxel, etoposide or beam radiation could trigger cell death in a similar fashion to HA14-1. Although partially blocked by Z-VAD-fmk, this effect was coincident to caspase-3 activation. Hence, we established that SV30-LNCs improved SV30 biological activity together with a potentiation of the mitochondrial membrane potential decrease. Interestingly, flow cytometry and confocal analysis indicated that SV30 itself conferred to LNCs improved mitochondrial targeting skills that may present a great interest toward the development of mitochondria targeted nanomedicines.

Dates et versions

hal-00842655 , version 1 (09-07-2013)

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Citer

M. Weyland, F. Manero, A. Paillard, Danielle Gree, Guillaume Viault, et al.. Mitochondrial targeting by use of lipid nanocapsules loaded with SV30, an analogue of the small-molecule Bcl-2 inhibitor HA14-1.. Journal of Controlled Release, 2011, 151 (1), pp.74-82. ⟨10.1016/j.jconrel.2010.11.032⟩. ⟨hal-00842655⟩
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