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基于脂质和聚合物的纳米胶束的细胞毒性、凋亡和遗传毒性作用:一项体外评估

Cytotoxic, Apoptotic and Genotoxic Effects of Lipid-Based and Polymeric Nano Micelles, an In Vitro Evaluation.

作者信息

Bahadori Fatemeh, Kocyigit Abdurrahim, Onyuksel Hayat, Dag Aydan, Topcu Gulacti

机构信息

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Bezmialem Vakif University, Fatih, Istanbul 34093, Turkey.

Department of Medical Biochemistry, Faculty of Medicine, Bezmialem Vakif University, Istanbul 34093, Turkey.

出版信息

Toxics. 2017 Dec 30;6(1):7. doi: 10.3390/toxics6010007.

Abstract

Self-assembly systems (SAS) mainly consist of micelles, and liposomes are the classes of Nano Drug Delivery Systems with superior properties compared to traditional therapeutics in targeting cancer tumors. All commercially available nano-formulations of chemotherapeutics currently consist of SAS. According to our knowledge, a specific toxicity comparison based on material differences has not yet been performed. The purpose of this study was to evaluate and compare the toxicity of two SAS consisting of Sterically Stabilized Micelles (SSM) made of a lipid-based amphiphilic distearoyl-sn-glycero-phosphatidylethanolamine-polyethylene glycol (PEG)-2000 and a polymeric micelle (PM) consisting of Y-shape amphiphilic block copolymer, synthesized using poly ε-caprolactone and PEG. The mechanism of cytotoxicity and genotoxicity of micelles on L-929 healthy mouse fibroblast cells was assessed using Sulforhodamine-B, WST-1, Acridine Orange/Ethidium Bromide and alkaline single-cell gel electrophoresis assays. Results showed that SSM in conc. of 40 mg/mL shows very low cytotoxicity at the end of 24, 48 and 72 h. The DNA damage caused by SSM was much lower than PM while the latter one showed significant toxicity by causing apoptosis with the ED50 value of 3 mg/mL. While the DNA damage caused by SSM was ignorable, some DNA chain breaks were detected on cells treated with PM.

摘要

自组装系统(SAS)主要由胶束组成,脂质体是一类纳米药物递送系统,与传统疗法相比,在靶向癌症肿瘤方面具有优越的性能。目前所有市售的化疗纳米制剂均由SAS组成。据我们所知,尚未基于材料差异进行特定的毒性比较。本研究的目的是评估和比较两种SAS的毒性,一种是由基于脂质的两亲性二硬脂酰-sn-甘油磷脂酰乙醇胺-聚乙二醇(PEG)-2000制成的空间稳定胶束(SSM),另一种是由使用聚ε-己内酯和PEG合成的Y形两亲性嵌段共聚物组成的聚合物胶束(PM)。使用磺酰罗丹明-B、WST-1、吖啶橙/溴化乙锭和碱性单细胞凝胶电泳试验评估胶束对L-929健康小鼠成纤维细胞的细胞毒性和遗传毒性机制。结果表明,浓度为40 mg/mL的SSM在24、48和72小时结束时显示出非常低的细胞毒性。SSM引起的DNA损伤远低于PM,而后者通过导致细胞凋亡显示出显著毒性,ED50值为3 mg/mL。虽然SSM引起的DNA损伤可忽略不计,但在用PM处理的细胞上检测到了一些DNA链断裂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbbc/5874780/61011c73c03d/toxics-06-00007-g001.jpg

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