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Open Access Research

Nanotoxicity comparison of four amphiphilic polymeric micelles with similar hydrophilic or hydrophobic structure

Bo Zhao1, Xue-Qing Wang1*, Xiao-You Wang1, Hua Zhang1, Wen-Bing Dai1, Jun Wang3, Zhen-Lin Zhong4, Hou-Nan Wu2* and Qiang Zhang1*

Author Affiliations

1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

2 Medical and Healthy Analytical Center, Peking University, Beijing 100191, China

3 National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China

4 Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, China

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Particle and Fibre Toxicology 2013, 10:47  doi:10.1186/1743-8977-10-47

Published: 3 October 2013

Abstract

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.

Keywords:
Nanotoxicity; Amphiphilic polymeric micelles; J774.A1 cells; Eahy.926 cells; KM mice