Cellular Uptake and Intracellular Cargo Release From Dextran Based Nanogel Drug Carriers.
Cellular Uptake and Intracellular Cargo Release From Dextran Based Nanogel Drug Carriers.
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DOI：
10.1115/1.4023246
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发表时间：
2013-02
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影响因子：
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通讯作者：
M. Carme Coll Ferrer;Peter Sobolewski;R. Composto;D. Eckmann
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作者：
M. Carme Coll Ferrer;Peter Sobolewski;R. Composto;D. Eckmann
纳米凝胶（NG）作为药物递送平台具有很大的前景。在这项工作中，我们研究了溶菌酶-葡聚糖纳米凝胶（LDNG）作为药物载体在体外使用两种细胞系的潜力：模型靶组织，人脐带静脉内皮细胞（HUVEC）和单核吞噬细胞系统（佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）刺激的THP-1细胞）的模型。以罗丹明标记的葡聚糖（LRDNG）为原料，通过Maillard反应和热凝胶化反应制备LDNG（100 nm），并负载荧光探针5-十六烷酰氨基荧光素（HAF）作为模拟药物。落射荧光显微镜证实HUVEC快速摄取LRDNG。虽然LysoTracker绿色染色表明LRDNG的溶酶体命运，模拟药物货物（HAF）广泛扩散内的细胞在15分钟内。流式细胞仪和共聚焦显微镜表明缓慢摄取PMA刺激的THP-1细胞中的LRDNG，只有41%的细胞含有LRDNG后24小时曝光。最后，在研究剂量（20 μg/ml）下，暴露于LRDNG 24 h不影响任一细胞类型的活力。在较高剂量（200 μg/ml）下，LRDNG导致HUVEC和THP-1的活力显著丧失，分别测量为30%和38%。总的来说，我们的研究结果表明LRDNG作为药物递送平台的巨大潜力，将简单的生产，快速摄取和靶细胞中的货物释放与“隐身”特性和低细胞毒性相结合。
Nanogels (NG) hold great promise as a drug delivery platform. In this work, we examine the potential of lysozyme-dextran nanogels (LDNG) as drug carriers in vitro using two cell lines: a model target tissue, human umbilical cord vein endothelial cells (HUVEC) and a model of the mononuclear phagocyte system (phorbol 12-myristate 13-acetate (PMA)-stimulated THP-1 cells). The LDNG (∼100 nm) were prepared with rhodamine-label dextran (LRDNG) via Maillard reaction followed by heat-gelation reaction and were loaded with a fluorescent probe, 5-hexadecanoylaminofluorescein (HAF), as a mock drug. Epifluorescence microscopy confirmed rapid uptake of LRDNG by HUVEC. Although LysoTracker Green staining indicated a lysosomal fate for LRDNG, the mock drug cargo (HAF) diffused extensively inside the cell within 15 min. Flow cytometry and confocal microscopy indicated slow uptake of LRDNG in PMA-stimulated THP-1 cells, with only 41% of cells containing LRDNG after 24 h exposure. Finally, 24 h exposure to LRDNG did not affect the viability of either cell type at the dose studied (20 μg/ml). At a higher dose (200 μg/ml), LRDNG resulted in a marked loss of viability of HUVEC and THP-1, measuring 30% and 38%, respectively. Collectively, our results demonstrate the great potential of LRDNG as a drug delivery platform, combining simple production, rapid uptake and cargo release in target cells with "stealth" properties and low cytotoxicity.