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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

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Abstract

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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Acknowledgements

This work was funded partly by the Comissão de Coordenação e Desenvolvimento Regional do Norte (CCDR-N) project “Nanotechnology based functional solutions” (No. NORTE01-0145-FEDER-000019). O. F. S. received a Marie Curie fellowship, EU-EC COFUND program “NanoTRAINforGrowth” (No. 600375). The authors wish to thank Enrique Carbo-Argibay (INL) and Oliver Schraidt (INL) for the assistance with the cryo-TEM imaging, and Edite Figueiras (INL) for technical support related to the FLIM experiments.

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  1. Ana R. Faria and Oscar F. Silvestre contributed equally to this work.

Authors and Affiliations

  1. Department of Nanophotonics, Ultrafast Bio- and Nanophotonics Group, INL - International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330, Braga, Portugal

    Ana R. Faria, Oscar F. Silvestre, Christian Maibohm, Ricardo M. R. Adão & Jana B. Nieder

  2. Department of Life Sciences, INL - International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330, Braga, Portugal

    Bruno F. B. Silva

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  1. Ana R. Faria
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Correspondence to Jana B. Nieder.

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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

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Faria, A.R., Silvestre, O.F., Maibohm, C. et al. 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. 12, 991–998 (2019). https://doi.org/10.1007/s12274-018-2231-5

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