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Size influences the cytotoxicity of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO2) nanoparticles

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Abstract

The aim of this study is to uncover the size influence of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO2) nanoparticles on their potential cytotoxicity. PLGA and TiO2 nanoparticles of three different sizes were thoroughly characterized before in vitro cytotoxic tests which included viability, generation of reactive oxygen species (ROS), mitochondrial depolarization, integrity of plasma membrane, intracellular calcium influx and cytokine release. Size-dependent cytotoxic effect was observed in both RAW264.7 cells and BEAS-2B cells after cells were incubated with PLGA or TiO2 nanoparticles for 24 h. Although PLGA nanoparticles did not trigger significantly lethal toxicity up to a concentration of 300 μg/ml, the TNF-α release after the stimulation of PLGA nanoparticles should not be ignored especially in clinical applications. Relatively more toxic TiO2 nanoparticles triggered cell death, ROS generation, mitochondrial depolarization, plasma membrane damage, intracellular calcium concentration increase and size-dependent TNF-α release, especially at a concentration higher than 100 μg/ml. These cytotoxic effects could be due to the size-dependent interaction between nanoparticles and biomolecules, as smaller particles tend to adsorb more biomolecules. In summary, we demonstrated that the ability of protein adsorption could be an important paradigm to predict the in vitro cytotoxicity of nanoparticles, especially for low toxic nanomaterials such as PLGA and TiO2 nanoparticles.

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Acknowledgments

Ms Xiong Sijing would like to acknowledge the Nanyang Technological University—Ian Ferguson Postgraduate Fellowship support for her research attachment to University of California, Los Angeles (UCLA). We thank Dr. Andre E. Nel and Dr. Tian Xian (UC Center for Environmental Implications of Nanotechnology) for their kind help in this study. Financial support from the following funding agencies (NMRC, A*STAR and NITHM) are also acknowledged: NMRC/EDG/0062/2009 and A*STAR Project No: 102 129 0098.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. School of Materials Science and Engineering, Nanyang Technological University, Block N4.1, 50 Nanyang Avenue, Singapore, 639798, Singapore

    Sijing Xiong, Haiyang Yu, Kee Woei Ng & Joachim Say-Chye Loo

  2. California NanoSystems Institute, University of California, Los Angeles, CA, 90095, USA

    Saji George, Robert Damoiseaux & Bryan France

  3. Centre for Sustainable Nanotechnology, School of Chemical and Life Sciences, Nanyang Polytechnic, Singapore, 569824, Singapore

    Saji George

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  1. Sijing Xiong
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  2. Saji George
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Correspondence to Joachim Say-Chye Loo.

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Xiong, S., George, S., Yu, H. et al. Size influences the cytotoxicity of poly (lactic-co-glycolic acid) (PLGA) and titanium dioxide (TiO2) nanoparticles. Arch Toxicol 87, 1075–1086 (2013). https://doi.org/10.1007/s00204-012-0938-8

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