Research Article

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2019, 12(5): 991–998

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https://doi.org/10.1007/s12274-018-2231-5

Cubosome nanoparticles for enhanced delivery of mitochondria anticancer drug elesclomol and therapeutic monitoring via sub-cellular NAD (P) H multi-photon fluorescence lifetime imaging

Ana R. Faria1,§, Oscar F. Silvestre1,§, Christian Maibohm1, Ricardo M. R. Ado1, Bruno F. B. Silva2, and Jana B. Nieder1 (*)

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1 Department of Nanophotonics, Ultrafast Bio- and Nanophotonics Group, INL - International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330 Braga, Portugal
2 Department of Life Sciences, INL - International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330 Braga, Portugal
§ Ana R. Faria and Oscar F. Silvestre contributed equally to this work.

Keywords: cubosomes, mitochondria, reactive oxygen species, elesclomol, NAD(P)H fluorescence lifetime, anticancer therapy
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  • Abstract
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Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen species. Here, for the first time, we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized with Pluronic F127. Cellular uptake and nanocarrier accumulation close to the mitochondria with sub-micrometer distance is identified via three-dimensional (3D) confocal microscopy and edge-to-edge compartment analysis. To monitor the therapeutic effect of the ELC nanocarrier, we apply for the first time, label-free time-lapse multi-photon fluorescence lifetime imaging microscopy (MP-FLIM) to track NAD(P)H cofactors with sub-cellular resolution on live cells exposed to an anticancer nanocarrier. Improved in vitro cytotoxicity is verified when loading the pre-complexed ELC with copper (ELC-Cu). Importantly, for equivalent copper concentration, cubosomes loaded with ELC-Cu show higher cytotoxicity compared to the free drug. The novel nanocarrier shows promising features for systemic ELC-Cu administration, and furthermore we establish the MP-FLIM technique for the assessment of anticancer drug delivery systems.
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Cubosome nanoparticles for enhanced delivery of mitochondria anticancer drug elesclomol and therapeutic monitoring via sub-cellular NAD (P) H multi-photon fluorescence lifetime imaging. Nano Res. 2019, 12(5): 991–998 https://doi.org/10.1007/s12274-018-2231-5

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