Abstract
Recent studies have revealed the existence of liver cancer stem cells (CSCs). Therefore, there is an urgent need for new and effective treatment strategies specific to liver CSCs. In this work, the poly(d,l-lactide-coglycolide) nanoparticles containing paclitaxel were prepared by emulsification-solvent evaporation method. The nanoparticles decorated with anti-CD133 antibody, termed targeted nanoparticles, were prepared by carbodiimide chemistry for liver CSCs. The physicochemical characteristics of the nanoparticles (i.e., encapsulation efficiency, particle size distribution, morphology, and in vitro release) were investigated. Cellular uptake and accumulation in tumor tissue of nanoparticles were observed. To assess anti-tumor activity of nanoparticles in vitro and in vivo, cell survival assay and tumor regression study were carried out using liver cancer cell lines (Huh7 and HepG2) and their xenografts. Particle size of targeted nanoparticles was 429.26 ± 41.53 nm with zeta potential of −11.2 mV. Targeted nanoparticles possessed spherical morphology and high encapsulation efficiency (87.53 ± 5.9 %). The accumulation of targeted nanoparticles depends on dual effects of passive and active targeting. Drug-loaded nanoparticles showed cytotoxicity on the tumor cells in vitro and in vivo. Targeted nanoparticles resulted in significant improvement in therapeutic response through selectively eliminating CD133 positive subpopulation. These results suggested that the novel nanoparticles could be a promising candidate with excellent therapeutic efficacy for targeting liver CSCs.
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Acknowledgments
This work was supported by National Nature Science Foundations of China: No. 81000987, China Postdoctoral Science Foundation Funded Project: No. 201003744, and China Shaanxi Provincial Science and Technology Coordinating Innovative Project: No. 2011KTCL03-15.
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Cheng Jin, Zhaoxu Yang, Jingyue Yang, Haimin Li, Yong He, Jiaze An and Ling Bai contributed equally to this work.
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Jin, C., Yang, Z., Yang, J. et al. Paclitaxel-loaded nanoparticles decorated with anti-CD133 antibody: a targeted therapy for liver cancer stem cells. J Nanopart Res 16, 2157 (2014). https://doi.org/10.1007/s11051-013-2157-5
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DOI: https://doi.org/10.1007/s11051-013-2157-5