Prolonged intracellular accumulation of light-inducible nanoparticles in leukemia cells allows their remote activation

Carlos Boto, Emanuel Quartin, Yijun Cai, Alberto Martín-Lorenzo, María Begoña García Cenador, Sandra Pinto, Rajeev Gupta, Tariq Enver, Isidro Sánchez-García, Dengli Hong, Ricardo Pires das Neves () and Lino Ferreira ()
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Carlos Boto: CNC-Center for Neurosciences and Cell Biology, University of Coimbra
Emanuel Quartin: CNC-Center for Neurosciences and Cell Biology, University of Coimbra
Yijun Cai: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine
Alberto Martín-Lorenzo: Experimental Therapeutics and Translational Oncology Program, Instituto de Biologia Molecular y Celular del Cancer (IBMCC), CSIC/University of Salamanca
María Begoña García Cenador: Institute of Biomedical Research of Salamanca (IBSAL)
Sandra Pinto: CNC-Center for Neurosciences and Cell Biology, University of Coimbra
Rajeev Gupta: UCL Cancer Institute, University College London
Tariq Enver: UCL Cancer Institute, University College London
Isidro Sánchez-García: Experimental Therapeutics and Translational Oncology Program, Instituto de Biologia Molecular y Celular del Cancer (IBMCC), CSIC/University of Salamanca
Dengli Hong: Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine
Ricardo Pires das Neves: CNC-Center for Neurosciences and Cell Biology, University of Coimbra
Lino Ferreira: CNC-Center for Neurosciences and Cell Biology, University of Coimbra

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract Leukaemia cells that are resistant to conventional therapies are thought to reside in protective niches. Here, we describe light-inducible polymeric retinoic acid (RA)-containing nanoparticles (NPs) with the capacity to accumulate in the cytoplasm of leukaemia cells for several days and release their RA payloads within a few minutes upon exposure to blue/UV light. Compared to NPs that are not activated by light exposure, these NPs more efficiently reduce the clonogenicity of bone marrow cancer cells from patients with acute myeloid leukaemia (AML) and induce the differentiation of RA-low sensitive leukaemia cells. Importantly, we show that leukaemia cells transfected with light-inducible NPs containing RA can engraft into bone marrow in vivo in the proximity of other leukaemic cells, differentiate upon exposure to blue light and release paracrine factors that modulate nearby cells. The NPs described here offer a promising strategy for controlling distant cell populations and remotely modulating leukaemic niches.

Date: 2017
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DOI: 10.1038/ncomms15204

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