Theranostics 2016; 6(9):1378-1392. doi:10.7150/thno.15156

Research Paper

Phenylboronic Acid-Mediated Tumor Targeting of Chitosan Nanoparticles

Xin Wang1,2, Huang Tang1, Chongzhi Wang1, Jialiang Zhang1, Wei Wu1, Xiqun Jiang1✉

1. Department of Polymer Science & Engineering, College of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210093, P. R. China.
2. Engineering Research Center for Biomedical Materials, School of Life Science, Anhui University, Hefei, 230601, P. R. China.


The phenylboronic acid-conjugated chitosan nanoparticles were prepared by particle surface modification. The size, zeta potential and morphology of the nanoparticles were characterized by dynamic light scattering, zeta potential measurement and transmission electron microscopy. The cellular uptake, tumor penetration, biodistribution and antitumor activity of the nanoparticles were evaluated by using monolayer cell model, 3-D multicellular spheroid model and H22 tumor-bearing mice. The incorporation of phenylboronic acid group into chitosan nanoparticles impart a surface charge-reversible characteristic to the nanoparticles. In vitro evaluation using 2-D and 3-D cell models showed that phenylboronic acid-decorated nanoparticles were more easily internalized by tumor cells compared to non-decorated chitosan nanoparticles, and could deliver more drug into tumor cells due to the active targeting effect of boronic acid group. Furthermore, the phenylboronic acid-decorated nanoparticles displayed a deeper penetration and persistent accumulation in the multicellular spheroids, resulting in better inhibition growth to multicellular spheroids than non-decorated nanoparticles. Tumor penetration, drug distribution and near infrared fluorescence imaging revealed that phenylboronic acid-decorated nanoparticles could penetrate deeper and accumulate more in tumor area than non-decorated ones. In vivo antitumor examination demonstrated that the phenylboronic acid-decorated nanoparticles have superior efficacy in restricting tumor growth and prolonging the survival time of tumor-bearing mice than free drug and drug-loaded chitosan nanoparticles.

Keywords: Chitosan nanoparticles, phenylboronic acid, 3-D multicellular spheroids, antitumor.

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How to cite this article:
Wang X, Tang H, Wang C, Zhang J, Wu W, Jiang X. Phenylboronic Acid-Mediated Tumor Targeting of Chitosan Nanoparticles. Theranostics 2016; 6(9):1378-1392. doi:10.7150/thno.15156. Available from