@article{Zhang2018, 
author = {Yapei Zhang and Yingying Li and Jinlong Ma and Xinyu Wang and Zhi Yuan and Wei Wang},
title = {Convenient preparation of charge-adaptive chitosan nanomedicines for extended blood circulation and accelerated endosomal escape},
year = {2018},
journal = {Nano Research},
volume = {11},
number = {8},
pages = {4278-4292},
keywords = {chitosan, poly(methyl methacrylate), blood circulation, charge reverse, endosomal escape},
url = {https://www.sciopen.com/article/10.1007/s12274-018-2014-z},
doi = {10.1007/s12274-018-2014-z},
abstract = {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.}
}