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Nano Research 2019, 12(5): 991-998 https://doi.org/10.1007/s12274-018-2231-5
Research Article | Issue | Published: 09 November 2018

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

Show Author's Information Ana R. Faria1,§,  Oscar F. Silvestre1,§,  Christian Maibohm1,  Ricardo M. R. Adão1,  Bruno F. B. Silva2,  Jana B. Nieder1( )
Department of Nanophotonics, Ultrafast Bio- and Nanophotonics Group,INL-International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330,Braga,Portugal;
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:
mitochondria, reactive oxygen species, cubosomes, elesclomol, NAD(P)H fluorescence lifetime, anticancer therapy
Topics:
CopperCytotoxicityFluorescence imagingPhotonsTargeted drug delivery
Cite this article:
Faria AR, Silvestre OF, 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 Research, 2019, 12(5): 991-998. https://doi.org/10.1007/s12274-018-2231-5
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Abstract Full text Electronic supplementary material About this article

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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Electronic supplementary material
About this article

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

Show Author's information Ana R. Faria1,§, Oscar F. Silvestre1,§, Christian Maibohm1, Ricardo M. R. Adão1, Bruno F. B. Silva2, Jana B. Nieder1( )
Department of Nanophotonics, Ultrafast Bio- and Nanophotonics Group,INL-International Iberian Nanotechnology Laboratory, Av. Mestre José Veiga s/n, 4715-330,Braga,Portugal;
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.

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.

Keywords: mitochondria, reactive oxygen species, cubosomes, elesclomol, NAD(P)H fluorescence lifetime, anticancer therapy

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Publication history
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Acknowledgements

Publication history

Received: 28 April 2018
Revised: 19 October 2018
Accepted: 21 October 2018
Published: 09 November 2018
Issue date: May 2019

Copyright

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

Acknowledgements

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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