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The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in astrocytes – electrophysiological quantification†
Biomaterials Science ( IF 5.8 ) Pub Date : 2017-12-27 00:00:00 , DOI: 10.1039/c7bm00886d Helena H. Chowdhury 1, 2, 3, 4, 5 , Susana R. Cerqueira 6, 7, 8, 9, 10 , Nuno Sousa 8, 11, 12, 13, 14 , Joaquim M. Oliveira 6, 7, 8, 9, 10 , Rui L. Reis 6, 7, 8, 9, 10 , Robert Zorec 1, 2, 3, 4, 5
Biomaterials Science ( IF 5.8 ) Pub Date : 2017-12-27 00:00:00 , DOI: 10.1039/c7bm00886d Helena H. Chowdhury 1, 2, 3, 4, 5 , Susana R. Cerqueira 6, 7, 8, 9, 10 , Nuno Sousa 8, 11, 12, 13, 14 , Joaquim M. Oliveira 6, 7, 8, 9, 10 , Rui L. Reis 6, 7, 8, 9, 10 , Robert Zorec 1, 2, 3, 4, 5
Affiliation
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Nanoparticle-based drug delivery systems may impose risks to patients due to potential toxicity associated with a lack of clearance from cells or prolonged carrier-cell retention. This work evaluates vesicular cell uptake, retention and the possible transfer of endocytosed methylprednisolone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (NPs) into secretory vesicles of rat cultured astrocytes. The cells were incubated with NPs and unitary vesicle fusions/fissions with the plasma membrane were monitored employing high-resolution membrane capacitance measurements. In the NP-treated cells the frequency of unitary exocytotic events was significantly increased. The presence of NPs also induces an increase in the size of exocytotic vesicles interacting with the plasma membrane, which exhibit transient fusion with prolonged fusion pore dwell-time. Live-cell confocal imaging revealed that once NPs internalize into endocytotic compartments they remain in the cell for 7 days, although a significant proportion of these merge with secretory vesicles destined for exocytosis. Co-localization studies show the route of clearance of NPs from cells via the exocytotic pathway. These findings bring new insight into the understanding of the intracellular trafficking and biological interactions of drug-loaded dendrimer NPs targeting astrocytes.
中文翻译：
星形胶质细胞中载有药物的树状大分子纳米颗粒的摄取，保留和清除–电生理定量†
基于纳米颗粒的药物递送系统可能由于与细胞清除能力不足或载体细胞保留时间延长相关的潜在毒性而给患者带来风险。这项工作评估囊泡细胞摄取，保留和内吞的甲基泼尼松龙负载的羧甲基壳聚糖/聚（酰胺基胺）树状大分子纳米颗粒（NPs）进入大鼠培养的星形胶质细胞的分泌囊泡的转移。将细胞与NP一起温育，并使用高分辨率膜电容测量监测与质膜的单囊泡融合/裂变。在NP处理的细胞中，单一胞吐事件的频率显着增加。NP的存在还诱导与胞膜相互作用的胞吐小泡大小的增加，表现出短暂的融合，并具有延长的融合孔停留时间。活细胞共聚焦成像显示，一旦NP内化进入胞吞区室，它们就会在细胞中保留7天，尽管其中很大一部分会与注定用于胞吐作用的分泌性囊泡融合。共定位研究表明从细胞清除NP的途径通过胞吐途径。这些发现为了解针对星形胶质细胞的载有药物的树状聚合物NPs的细胞内运输和生物学相互作用的理解提供了新的见识。
更新日期：2017-12-27
中文翻译：
星形胶质细胞中载有药物的树状大分子纳米颗粒的摄取，保留和清除–电生理定量†
基于纳米颗粒的药物递送系统可能由于与细胞清除能力不足或载体细胞保留时间延长相关的潜在毒性而给患者带来风险。这项工作评估囊泡细胞摄取，保留和内吞的甲基泼尼松龙负载的羧甲基壳聚糖/聚（酰胺基胺）树状大分子纳米颗粒（NPs）进入大鼠培养的星形胶质细胞的分泌囊泡的转移。将细胞与NP一起温育，并使用高分辨率膜电容测量监测与质膜的单囊泡融合/裂变。在NP处理的细胞中，单一胞吐事件的频率显着增加。NP的存在还诱导与胞膜相互作用的胞吐小泡大小的增加，表现出短暂的融合，并具有延长的融合孔停留时间。活细胞共聚焦成像显示，一旦NP内化进入胞吞区室，它们就会在细胞中保留7天，尽管其中很大一部分会与注定用于胞吐作用的分泌性囊泡融合。共定位研究表明从细胞清除NP的途径通过胞吐途径。这些发现为了解针对星形胶质细胞的载有药物的树状聚合物NPs的细胞内运输和生物学相互作用的理解提供了新的见识。
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