|Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure|
|Zhao, Bo1; Wang, Xue-Qing1; Wang, Xiao-You1; Zhang, Hua1; Dai, Wen-Bing1; Wang, Jun3,4; Zhong, Zhen-Lin5; Wu, Hou-Nan2; Zhang, Qiang1|
|关键词||Nanotoxicity Amphiphilic polymeric micelles J774.A1 cells Eahy.926 cells KM mice|
|刊名||PARTICLE AND FIBRE TOXICOLOGY|
|WOS标题词||Science & Technology|
|关键词[WOS]||DRUG-DELIVERY ; ENGINEERED NANOMATERIALS ; CARBON NANOTUBES ; IN-VIVO ; DIFFERENT SIZES ; RISK-ASSESSMENT ; NANOPARTICLES ; CYTOTOXICITY ; TOXICITY ; TRANSPORT|
Background: Nanocarriers represent an attractive means of drug delivery, but their biosafety must be established before their use in clinical research.
Objectives: Four kinds of amphiphilic polymeric (PEG-PG-PCL, PEEP-PCL, PEG-PCL and PEG-DSPE) micelles with similar hydrophilic or hydrophobic structure were prepared and their in vitro and in vivo safety were evaluated and compared.
Methods: In vitro nanotoxicity evaluations included assessments of cell morphology, cell volume, inflammatory effects, cytotoxicity, apoptosis and membrane fluidity. An umbilical vein cell line (Eahy.926) and a kind of macrophages (J774.A1) were used as cell models considering that intravenous route is dominant for micelle delivery systems. In vivo analyses included complete blood count, lymphocyte subset analysis, detection of plasma inflammatory factors and histological observations of major organs after intravenous administration to KM mice.
Results: All the micelles enhanced inflammatory molecules in J774.A1 cells, likely resulting from the increased ROS levels. PEG-PG-PCL and PEEP-PCL micelles were found to increase the J774.A1 cell volume. This likely correlated with the size of PEG-PG-PCL micelles and the polyphosphoester structure in PEEP-PCL. PEG-DSPE micelles inhibited the growth of Eahy.926 cells via inducing apoptosis. This might relate to the structure of DSPE, which is a type of phospholipid and has good affinity with cell membrane. No evidence was found for cell membrane changes after treatment with these micelles for 24 h. In the in vivo study, during 8 days of 4 time injection, each of the four nanocarriers altered the hematic phase differently without changes in inflammatory factors or pathological changes in target organs.
Conclusions: These results demonstrate that the micelles investigated exhibit diverse nanotoxicity correlated with their structures, their biosafety is different in different cell model, and there is no in vitro and in vivo correlation found. We believe that this study will certainly provide more scientific understandings on the nanotoxicity of amphiphilic polymeric micelles.
|项目编号||2009CB930300 ; 81273456 ; 81130059 ; BMU20110263|
|资助机构||National Basic Research Program of China ; National Natural Science Foundation of China ; Innovation Team of Ministry of Education|
|作者单位||1.Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China|
2.Peking Univ, Med & Hlth Analyt Ctr, Beijing 100191, Peoples R China
3.Univ Sci & Technol China, Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China
4.Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China
5.Wuhan Univ, Dept Chem, Key Lab Biomed Polymers, Minist Educ, Wuhan 430072, Peoples R China
|Zhao, Bo,Wang, Xue-Qing,Wang, Xiao-You,et al. Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure[J]. PARTICLE AND FIBRE TOXICOLOGY,2013,10.|
|APA||Zhao, Bo.,Wang, Xue-Qing.,Wang, Xiao-You.,Zhang, Hua.,Dai, Wen-Bing.,...&Zhang, Qiang.(2013).Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure.PARTICLE AND FIBRE TOXICOLOGY,10.|
|MLA||Zhao, Bo,et al."Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure".PARTICLE AND FIBRE TOXICOLOGY 10(2013).|