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Surface modification of paclitaxel-loaded tri-block copolymer PLGA-b-PEG-b-PLGA nanoparticles with protamine for liver cancer therapy

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Abstract

In order to enhance the therapeutic effect of chemotherapy on liver cancer, a biodegradable formulation of protamine-modified paclitaxel-loaded poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-b-PEG-b-PLGA) nanoparticles (PTX-loaded/protamine NPs) was prepared. Tri-block copolymer PLGA-b-PEG-b-PLGA was synthesized by ring-opening polymerization and characterized by 1H NMR spectroscopy and gel permeation chromatography. PTX-loaded and PTX-loaded/protamine NPs were characterized in terms of size, size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin 6-loaded/protamine NPs were internalized by hepatocellular carcinoma cell line HepG2. The cellular uptake efficiency of NPs was obviously elevated after protamine modification. With commercial formulation Taxol® as the reference, HepG2 cells were also used to study the cytotoxicity of the NPs. PTX-loaded/protamine NPs exhibited significantly higher cytotoxicity than PTX-loaded NPs and Taxol® did. All the results suggested that surface modification of PTX-loaded PLGA-b-PEG-b-PLGA NPs with protamine boosted the therapeutic efficacy on liver cancer.

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Acknowledgments

The authors are grateful for financial support from the National Natural Science Foundation of China (No. 51203085, 31270019, and 81302553), National High-Tech Research and development program (No. 2015AA020316), Guangdong Natural Science Funds for Distinguished Young Scholar (No. 2014A030306036), Scientific and Technological Innovation Bureau of Nanshan District (No. KC2014JSCX0023A), Natural Science Foundation of Guangdong Province (No. 2015A030313848), Shenzhen Peacock Innovation Team (No. 110811003586331) and Shenzhen Key Laboratory of Marine Biomedical Materials (No. ZDSY20130401165820356).

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    Authors and Affiliations

    1. Research Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, 518055, People’s Republic of China

      Nansha Gao & Changshun Ruan

    2. Analysis Centre, Guangdong Medical College, Dongguan, 523808, People’s Republic of China

      Zhihong Chen

    3. The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055, People’s Republic of China

      Lin Mei & Xiaowei Zeng

    4. Institute of Allergy and Immunology, School of Medicine, Shenzhen University, Shenzhen, 518060, People’s Republic of China

      Xiaojun Xiao & Zhigang Liu

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    1. Nansha Gao
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    2. Zhihong Chen
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    Correspondence to Zhigang Liu or Xiaowei Zeng.

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    Nansha Gao, Zhihong Chen, and Xiaojun Xiao have contributed equally to this work.

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    Gao, N., Chen, Z., Xiao, X. et al. Surface modification of paclitaxel-loaded tri-block copolymer PLGA-b-PEG-b-PLGA nanoparticles with protamine for liver cancer therapy. J Nanopart Res 17, 347 (2015). https://doi.org/10.1007/s11051-015-3121-3

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