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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

  • Ana R. Faria
  • Oscar F. Silvestre
  • Christian Maibohm
  • Ricardo M. R. Adão
  • Bruno F. B. Silva
  • Jana B. NiederEmail author
Research Article
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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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Keywords

cubosomes mitochondria reactive oxygen species elesclomol NAD(P)H fluorescence lifetime anticancer therapy 
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Notes

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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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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© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Ana R. Faria
    • 1
  • Oscar F. Silvestre
    • 1
  • Christian Maibohm
    • 1
  • Ricardo M. R. Adão
    • 1
  • Bruno F. B. Silva
    • 2
  • Jana B. Nieder
    • 1
    Email author
  1. 1.Department of Nanophotonics, Ultrafast Bio- and Nanophotonics GroupINL - International Iberian Nanotechnology LaboratoryBragaPortugal
  2. 2.Department of Life SciencesINL - International Iberian Nanotechnology LaboratoryBragaPortugal

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