Author(s):
Boto, Carlos ; Quartin, Emanuel ; Cai, Yijun ; Martín-Lorenzo, Alberto ; Cenador, María Begoña García ; Pinto, Sandra ; Gupta, Rajeev ; Enver, Tariq ; Sánchez-García, Isidro ; Hong, Dengli ; Neves, Ricardo Pires das ; Ferreira, Lino
Date: 2017
Persistent ID: https://hdl.handle.net/10316/108282
Origin: Estudo Geral - Universidade de Coimbra
Project/scholarship:
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/PT;
Subject(s): Aged; Aged, 80 and over; Animals; Benzene Derivatives; Cell Line, Tumor; Drug Compounding; Female; Formates; Human Umbilical Vein Endothelial Cells; Humans; Leukemia, Promyelocytic, Acute; Leukocytes; Light; Male; Mice; Mice, Inbred NOD; Nanoparticles; Photosensitizing Agents; Polyethyleneimine; Tretinoin; U937 Cells; Xenograft Model Antitumor Assays
Description
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.
We acknowledge the use of the Laborato´rio de Bio-imagem de Alta Resoluc¸a˜o of the Faculty of Medicine of University of Coimbra. The authors would like to thank the financial support of FEDER through the programme COMPETE and by Portuguese funds through FCT (PTDC/CTM-NAN/120552/2010 and UID/NEU/04539/2013 to R.P.N.), FCT (SFRH/BD/62419/2009 to C.B.; SFRH/BD/90964/2012 to E.Q.; POCI-01-0145-FEDER-016390:CANCEL STEM to L.F.), EC (ERC project n 307384, ‘Nanotrigger’ to L.F.), MINECO (SAF2012-32810, SAF2015-64420-R and Red de Excelencia Consolider OncoBIO SAF2014-57791-REDC to I.S.-G.) and Bloodwise and CRUK programme grants to T.E.
