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首页> 外文期刊>ACS Macro Letters >Facile Dye-Initiated Polymerization of Lactide-Glycolide Generates Highly Fluorescent Poly(lactic-co-glycolic Acid) for Enhanced Characterization of Cellular Delivery
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Facile Dye-Initiated Polymerization of Lactide-Glycolide Generates Highly Fluorescent Poly(lactic-co-glycolic Acid) for Enhanced Characterization of Cellular Delivery

机译：丙交酯 - 乙酰胺的容易染料引发的聚合产生高荧光聚（乳酸二乙醇酸），以提高细胞递送的表征

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Poly(lactic-co- ycolic acid) (PLGA) is a versatile synthetic copolymer that is widely used in pharmaceutical applications. This is because it is well-tolerated in the body, and copolymers of varying physicochemical properties are readily available via ring-opening polymerization. However, native PLGA polymers are hard to track as drug delivery carriers when delivered to subcellular spaces, due to the absence of an easily accessible "handle" for fluorescent labeling. Here we show a one-step, scalable, solvent-free, synthetic route to fluorescent blue (2-aminoanthracene), green (5-aminofluorescein), and red (rhodamine-6G) PLGA, in which every polymer chain in the sample is fluorescently labeled. The utility of initiator-labeled PLGA was demonstrated through the preparation of nanopartides, capable of therapeutic subcellular delivery to T-helper-precursor-1 (THP-1) macrophages, a model cell line for determining in vitro biocompatibility and particle uptake. Super resolution confocal fluorescence microscopy imaging showed that dye-initiated PLGA nanoparticles were internalized to punctate regions and retained bright fluorescence over at least 24 h. In comparison, PLGA nanoparticles with S-aminofluorescein introduced by conventional nanoprecipitation/encapsulation showed diffuse and much lower fluorescence intensity in the same cells and over the same time periods. The utility of this approach for in vitro drug delivery experiments was demonstrated through the concurrent imaging of the fluorescent drug doxorubicin (lambda(ex) = 480 nm, lambda(em) = 590 nm) with carrier 5-aminofluorescein PLGA, also in THP-1 cells, in which the intracellular locations of the drug and the polymer could be dearly visualized. Finally, the dye-labeled partides were evaluated in an in vivo model, via delivery to the nematode Caenorhabditis elegans, with bright fluorescence again apparent in the internal tract after 3 h. The results presented in this manuscript highlight the ease of synthesis of highly fluorescent PLGA, which could be used to augment tracking of future therapeutics and accelerate in vitro and in vivo characterization of delivery systems prior to dinical translation.
机译：聚（乳酸共同酸）（PLGA）是一种广泛应用于药物应用的通用合成共聚物。这是因为它在体内有良好耐受，并且可以通过开环聚合容易地获得不同的物理化学性质的共聚物。然而，由于没有用于荧光标记的易于接近的“手柄”，天然PLGA聚合物在递送到亚细胞空间时难以跟踪药物输送载体。在这里，我们展示了一步，可扩展，无溶剂，合成的荧光蓝（2-氨基蒽），绿色（5-氨基荧光素）和红色（罗丹明-6G）PLGA，其中样品中的每种聚合物链是荧光标记。通过制备纳米丙糖苷来证明引发剂标记的PLGA的效用，能够治疗亚细胞输送到T-辅助 - 前体-1（THP-1）巨噬细胞，用于确定体外生物相容性和颗粒摄取的模型细胞系。超分辨率共聚焦荧光显微镜成像表明，染料引发的PLGA纳米颗粒内化至点状区，并在至少24小时内保留明亮的荧光。相比之下，通过常规纳米沉淀/包封引入的具有S-氨基荧光蛋白的PLGA纳米粒子显示在同一细胞中并在同一时间段内显示弥漫性和更低的荧光强度。通过荧光药物Doxorubicin的并发成像（Lambda（ex）= 480nm，λ（em）= 590nm）与载体5- aminofologercein plga的同时成像，还证明了这种方法对体外药物递送实验的效用。 1个细胞，其中药物和聚合物的细胞内位置可以是珍贵的。最后，在体内模型中，通过递送至线虫乳房杆菌的侧视杆，在3小时后在内部道中再次显而易见，在体内模型中评价染料标记的偏见。本手稿中提出的结果突出了高度荧光PLGA的易于合成，可用于增加未来治疗剂的跟踪，并在多种翻译之前在体外加速和体内表征递送系统。

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    《ACS Macro Letters》 |2020年第3期|共7页
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