Convenient preparation of charge-adaptive chitosan nanomedicines for extended blood circulation and accelerated endosomal escape

  • Yapei Zhang
  • Yingying Li
  • Jinlong Ma
  • Xinyu Wang
  • Zhi Yuan
  • Wei Wang
Research Article


A major impediment in the development of chitosan nanoparticles (CTS NPs) as effective drug delivery vesicles is their rapid clearance from blood and endosome entrapment. To overcome these problems, a convenient and promising template system was developed by decorating poly(methacrylic acid) (PMAA) to the surface of 10-hydroxy camptothecin (HCPT)-loaded CTS NPs (HCPT-CTS/PMAA NPs). The results show that the presence of negatively charged PMAA significantly elongated the blood circulation time of HCPT-CTS NPs from 12 to 24 h, and reduced the blood clearance (Cl) from 30.57 to 6.72 mL/h in vivo. The calculated area under curve (AUC0-24h) and terminal elimination half-life (t1/2) of HCPT-CTS/PMAA NPs were 4.37-fold and 2.48-fold compared with those of HCPT-CTS NPs. Furthermore, the positively charged HCPT-CTS/PMAA NPs triggered by tumor acidic microenvironment (pH 6.5) result in a 453-fold higher cellular uptake than the negatively charged counterparts at pH 7.4. Additionally, HCPT-CTS/PMAA NPs have the ability to escape endosomal entrapment via “proton sponge effect” after incubation with HepG2 cells for 3 h at pH 6.5. Taken together, these findings open up a convenient, low-cost, but effective way to prepare HCPT-CTS/PMAA NPs as a candidate for developing vectors with enhanced long blood circulation and endosomal escape ability in future clinical experiments.


chitosan poly(methyl methacrylate) blood circulation charge reverse endosomal escape 


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This work was supported by the National Natural Science Foundation of China (Nos. 51433004 and 51773096), Natural Science Foundation of Tianjin (No. 17JCZDJC3 3500), PCSIRT (No. IRT1257). We also appreciate Prof. Deling Kong at Nankai University for help with the cellular experiments and Prof. Qiang Wu at Nankai University for help with the characterization of materials.

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Convenient preparation of charge-adaptive chitosan nanomedicines for extended blood circulation and accelerated endosomal escape


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Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Yapei Zhang
    • 1
  • Yingying Li
    • 1
  • Jinlong Ma
    • 1
  • Xinyu Wang
    • 1
  • Zhi Yuan
    • 1
    • 2
  • Wei Wang
    • 1
  1. 1.Key Laboratory of Functional Polymer Materials of the Ministry of Education, Institute of Polymer Chemistry, College of ChemistryNankai UniversityTianjinChina
  2. 2.Collaborative Innovation Center of Chemical Science and EngineeringNankai UniversityTianjinChina

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