Mechanistic investigation of cellular internalization routes of polymeric particles on breast cancer cells: relevance for drug delivery applications
Mechanistic investigation of cellular internalization routes of polymeric particles on breast cancer cells: relevance for drug delivery applications
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乳腺癌细胞上聚合物颗粒的细胞内化途径的机制研究：与药物输送应用的相关性
DOI：
10.1007/s13204-020-01376-0
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发表时间：
2020-04
期刊：
影响因子：
--
通讯作者：
徐峰
中科院分区：
文献类型：
--
作者：
周美容;谢萍芳;龚嘉;吴玉芳;裴雷;陈洁;徐峰
物理化学性质的调整，如颗粒大小，表面改性等，对于提高递送效率而具有微不足道的毒性至关重要。对荧光标记的聚苯乙烯颗粒[50和500 nm普通和200 nm和1 µm羧酸盐包被的聚苯乙烯（PPS和CPS）]对乳腺癌细胞的细胞摄取和细胞内运输进行了定量和机制研究。细胞增殖、活力和细胞毒性的检查表明，除了部分降低细胞活力的200 nm CPS（16 µg/mL）外，4-40 µg/mL浓度的聚合物颗粒对细胞无毒。定量荧光显微镜显示，200 nm CPS显示出被MCF-7细胞内化的最高能力，其中平均细胞内颗粒分别比1 µm CPS和500 nm PPS高约14倍和35倍。使用抑制剂对摄取途径的分析提供了明确的证据，即200 CPS主要通过网格蛋白介导的内吞作用摄入，而较大的颗粒（> 500 nm）优先利用巨胞饮途径。荧光活细胞成像表明，颗粒主要是由细胞在一个单独的形式，而不是大的聚集体内化，尽管在细胞质中的部分凝聚后期发生。总的来说，这些结果增强了我们对聚合物递送载体用于治疗乳腺癌的应用的理解。
The tuning of physicochemical properties like particle sizes, surface modifications, etc., is essential to improve delivery efficiency with insignificant toxicity. A quantitative and mechanistic investigation on cellular uptake and intracellular trafficking of fluorescent-labeled polystyrene particles [50 and 500 nm plain and 200 nm and 1 µm carboxylate-coated polystyrene (PPS and CPS)] against breast cancer cells was performed. Examinations of cell proliferation, viability, and cytotoxicity indicated that those applied polymeric particles at concentrations of 4–40 µg/mL are non-toxic to cells except 200 nm CPS (16 µg/mL) which partially reduced cell viability. Quantitative fluorescent microscopy revealed that 200 nm CPS displayed the highest capability to be internalized by MCF-7 cells, in which the average intracellular particles are about 14 and 35 folds higher than 1 µm CPS and 500 nm PPS, respectively. Analysis of the uptake routes using inhibitors provided clear evidence that 200 CPS was mainly ingested via the clathrin-mediated endocytosis, whereas larger particles (> 500 nm) preferentially utilized the macropinocytosis pathway. Fluorescent live-cell imaging suggested that particles were mainly internalized by cells in an individual form instead of large aggregates, despite late occurrence of partial agglomeration in the cytoplasm. Overall, those outcomes enhanced our understanding of the application of polymeric delivery vehicles for the treatment of breast cancer.
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影响因子：
10.2
作者：
Calero M;Chiappi M;Lazaro-Carrillo A;Rodríguez MJ;Chichón FJ;Crosbie-Staunton K;Prina-Mello A;Volkov Y;Villanueva A;Carrascosa JL
通讯作者：
Carrascosa JL
DOI：
10.1186/bcr2572
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Alvarez RH
通讯作者：
Alvarez RH
在纳米级的切割深处，高速刮擦的一种新型方法。
影响因子：
4.6
作者：
Zhang Z;Guo D;Wang B;Kang R;Zhang B
通讯作者：
Zhang B
影响因子：
8
作者：
Jiang L;Li X;Liu L;Zhang Q
通讯作者：
Zhang Q
影响因子：
12.6
作者：
Hu YB;Dammer EB;Ren RJ;Wang G
通讯作者：
Wang G