CNC-Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
3Is-Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal.
Nat Commun. 2017 May 11;8:15204. doi: 10.1038/ncomms15204.
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.
白血病细胞对常规疗法有耐药性，被认为存在于保护性龛位中。在这里，我们描述了一种光诱导的含有聚合维甲酸（RA）的纳米颗粒（NPs），它能够在几天内在白血病细胞的细胞质中积累，并在暴露于蓝/紫外光后几分钟内释放其 RA 有效载荷。与未受光激活的 NPs 相比，这些 NPs 更有效地降低了来自急性髓细胞性白血病（AML）患者的骨髓癌细胞的集落形成能力，并诱导 RA 低敏感白血病细胞的分化。重要的是，我们表明，用含有 RA 的光诱导 NPs 转染的白血病细胞可以在体内与其他白血病细胞邻近植入骨髓，在暴露于蓝光后分化，并释放旁分泌因子来调节附近的细胞。这里描述的 NPs 为控制远处细胞群体和远程调节白血病龛位提供了一种很有前途的策略。
