Interactions of polymeric drug carriers with DDT reduce their combined cytotoxicity
Interactions of polymeric drug carriers with DDT reduce their combined cytotoxicity
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聚合物药物载体与DDT的相互作用降低了它们的联合细胞毒性
DOI：
10.1016/j.envpol.2018.06.010
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发表时间：
2018
影响因子：
8.9
通讯作者：
Xing Baoshan
中科院分区：
文献类型：
--
作者：
Zhang Xuejiao;Lei Lei;Zhang Haiyan;Zhang Siyu;Xing Weiwei;Wang Jin;Li Haibo;Zhao Qing;Xing Baoshan
纳米药物的环境分布和命运已引起人们的关注。然而，它们对环境污染物毒性的影响却缺乏认识。本研究合成了带负电荷的聚（乙二醇）-b-聚（l -丙交酯-共乙二醇酸酯）（mPEG-PLA）和带正电荷的聚亚胺-棕榈酸酯（PEI-PA）纳米胶束，并作为模型药物载体，研究其与二氯二苯三氯乙烷（DDT）的相互作用和联合毒性。石英晶体耗散微天平（QCM-D）监测结果显示，DDT对mPEG-PLA纳米胶束的生物界面行为影响有限，而对PEI-PA纳米胶束在模型细胞膜上的附着有明显的抑制作用。实时细胞分析（RTCA）结果显示，与纳米胶束共处理或预处理后，DDT对NIH 3T3细胞的细胞毒性均显著降低。通过与mPEG-PLA纳米胶束共处理，DDT暴露的NIH 3T3细胞活力可提高90%。提出了三种可能的原因：(1)细胞培养基中游离滴滴涕的减少是由于滴滴涕被分成纳米胶束；(2)纳米胶团-滴滴涕配合物的细胞摄取由于配合物与细胞膜之间的复杂团聚或静电排斥而减轻；(3)溶酶体对纳米微粒- ddt复合物内吞的解毒作用。
Attention has been paid to the environmental distribution and fate of nanomedicines. However, their effects on the toxicity of environmental pollutants are lack of knowledge. In this study, the negatively charged poly (ethylene glycol)-b-poly (L-lactide-co-glycolide) (mPEG-PLA) and positively charged polyethyleneimine-palmitate (PEI-PA) nanomicelles were synthesized and served as model drug carriers to study the interaction and combined toxicity with dichlorodiphenyltrichloroethane (DDT). DDT exerted limited effect on the biointerfacial behavior of mPEG-PLA nanomicelles, whereas it significantly mitigated the attachment of PEI-PA nanomicelles on the model cell membrane as monitored by quartz crystal microbalance with dissipation (QCM-D). The cytotoxicity of DDT towards NIH 3T3 cells was greatly decreased by either co-treatment or pre-treatment with the nanomicelles according to the results of real-time cell analysis (RTCA). The cell viability of NIH 3T3 exposed to DDT was increased up to 90% by the co-treatment with mPEG-PLA nanomicelles. Three possible reasons were proposed: (1) decreased amount of free DDT in the cell culture medium due to the partitioning of DDT into nanomicelles; (2) mitigated cellular uptake of nanomicelle-DDT complexes due to the complex agglomeration or electrostatic repulsion between complexes and cell membrane; (3) detoxification effect in the lysosome upon endocytosis of nanomicelle-DDT complexes.